                         SEQUENCE LISTING

<110>  DiMarchi, Richard
       Li, Pengyun
 
<120>  CTP-BASED INSULIN ANALOGS FOR TREATMENT OF DIABETES

<130>  32993-223503

<150>  US 61/578,052
<151>  2011-12-20

<160>  104   

<170>  PatentIn version 3.5

<210>  1
<211>  21
<212>  PRT
<213>  Homo sapiens

<400>  1

Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser Leu Tyr Gln Leu 
1               5                   10                  15      


Glu Asn Tyr Cys Asn 
            20      


<210>  2
<211>  30
<212>  PRT
<213>  Homo sapiens

<400>  2

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Pro Lys Thr 
            20                  25                  30  


<210>  3
<211>  70
<212>  PRT
<213>  Homo sapiens

<400>  3

Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe 
1               5                   10                  15      


Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly 
            20                  25                  30          


Ser Ser Ser Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys Cys 
        35                  40                  45              


Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu 
    50                  55                  60                  


Lys Pro Ala Lys Ser Ala 
65                  70  


<210>  4
<211>  67
<212>  PRT
<213>  Homo sapiens

<400>  4

Ala Tyr Arg Pro Ser Glu Thr Leu Cys Gly Gly Glu Leu Val Asp Thr 
1               5                   10                  15      


Leu Gln Phe Val Cys Gly Asp Arg Gly Phe Tyr Phe Ser Arg Pro Ala 
            20                  25                  30          


Ser Arg Val Ser Arg Arg Ser Arg Gly Ile Val Glu Glu Cys Cys Phe 
        35                  40                  45              


Arg Ser Cys Asp Leu Ala Leu Leu Glu Thr Tyr Cys Ala Thr Pro Ala 
    50                  55                  60                  


Lys Ser Glu 
65          


<210>  5
<211>  21
<212>  PRT
<213>  Homo sapiens

<400>  5

Gly Ile Val Asp Glu Cys Cys Phe Arg Ser Cys Asp Leu Arg Arg Leu 
1               5                   10                  15      


Glu Met Tyr Cys Ala 
            20      


<210>  6
<211>  29
<212>  PRT
<213>  Homo sapiens

<400>  6

Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Tyr Leu 
1               5                   10                  15      


Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr 
            20                  25                  


<210>  7
<211>  21
<212>  PRT
<213>  Homo sapiens

<400>  7

Gly Ile Val Glu Glu Cys Cys Phe Arg Ser Cys Asp Leu Ala Leu Leu 
1               5                   10                  15      


Glu Thr Tyr Cys Ala 
            20      


<210>  8
<211>  32
<212>  PRT
<213>  Homo sapiens

<400>  8

Ala Tyr Arg Pro Ser Glu Thr Leu Cys Gly Gly Glu Leu Val Asp Thr 
1               5                   10                  15      


Leu Tyr Leu Val Cys Gly Asp Arg Gly Phe Tyr Phe Ser Arg Pro Ala 
            20                  25                  30          


<210>  9
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  spacer sequence

<400>  9

Pro Gly Pro Glu 
1               


<210>  10
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  spacer sequence

<400>  10

Phe Val Asn Gln 
1               


<210>  11
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  spacer sequence

<400>  11

Ala Tyr Arg Pro Ser Glu 
1               5       


<210>  12
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  spacer sequence

<400>  12

Tyr Thr Pro Lys Thr 
1               5   


<210>  13
<211>  12
<212>  PRT
<213>  Homo sapiens

<400>  13

Gly Tyr Gly Ser Ser Ser Arg Arg Ala Pro Gln Thr 
1               5                   10          


<210>  14
<211>  8
<212>  PRT
<213>  Homo sapiens

<400>  14

Gly Tyr Gly Ser Ser Ser Arg Arg 
1               5               


<210>  15
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Analog of the insulin A chain


<220>
<221>  MISC_FEATURE
<222>  (4)..(4)
<223>  Xaa at position 4 is aspartic acid or glutamic acid

<220>
<221>  MISC_FEATURE
<222>  (8)..(8)
<223>  Xaa at position 8 is histidine, threonine or phenylalanine

<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  Xaa at position 9 is serine, arginine, ornithine, lysine or 
       alanine

<220>
<221>  MISC_FEATURE
<222>  (14)..(14)
<223>  Xaa at position 14 is tyrosine, arginine, ornathine, lysine or 
       alanine

<220>
<221>  MISC_FEATURE
<222>  (15)..(15)
<223>  Xaa at position 15 is glutamine, glutamic acid, arginine, 
       ornithine, alanine, lysine or leucine

<220>
<221>  MISC_FEATURE
<222>  (17)..(17)
<223>  Xaa at position 17 is glutamine or glutamic acid

<220>
<221>  MISC_FEATURE
<222>  (18)..(18)
<223>  Xaa at position 18 is methionine, asparagine, glutamine, glutamic
       acid, aspartic acid or threonine

<220>
<221>  MISC_FEATURE
<222>  (19)..(19)
<223>  Xaa at position19 is tyrosine, 4-methoxy phenylalanine  or 
       4-amino-phenylalanine

<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  Xaa at position 21 is alanine, glycine, serine, valine, 
       threonine, isoleucine, leucine, glutamine, glutamic acid, 
       asparagine, aspartic acid, histidine, tryptophan, tyrosine, or 
       methionine

<400>  15

Gly Ile Val Xaa Glu Cys Cys Xaa Xaa Ser Cys Asp Leu Xaa Xaa Leu 
1               5                   10                  15      


Xaa Xaa Xaa Cys Xaa 
            20      


<210>  16
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Analog of the insulin B chain


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  Xaa at position 1 is histidine or threonine

<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  Xaa at position 5 is alanine, glycine or serine

<220>
<221>  MISC_FEATURE
<222>  (6)..(6)
<223>  Xaa at position 6 is histidine, aspartic acid, glutamic acid, 
       homocysteic acid or cysteic acid

<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  Xaa at position 9 is aspartic acid, glutamine or glutamic acid

<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  Xaa at position 10 is alanine or threonine

<220>
<221>  MISC_FEATURE
<222>  (12)..(12)
<223>  Xaa at position 12 is tyrosine or 4-amino-phenylalanine

<220>
<221>  MISC_FEATURE
<222>  (17)..(17)
<223>  Xaa at position 12 is glutamic acid, aspartic acid or asparagine

<220>
<221>  MISC_FEATURE
<222>  (18)..(18)
<223>  Xaa at position 18 is alanine, ornithine, lysine or arginine

<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  Xaa at position 21 is tyrosine, phenylalanine or 
       4-amino-phenylalanine

<400>  16

Xaa Leu Cys Gly Xaa Xaa Leu Val Xaa Xaa Leu Xaa Leu Val Cys Gly 
1               5                   10                  15      


Asp Xaa Gly Phe Xaa 
            20      


<210>  17
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Analog of the insulin B chain


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  Xaa at position 1 is histidine or threonine

<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  Xaa at position 5 is alanine, glycine or serine

<220>
<221>  MISC_FEATURE
<222>  (6)..(6)
<223>  Xaa at position 6 is histidine, aspartic acid, glutamic acid, 
       homocysteic acid or cysteic acid

<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  Xaa at position 9 is aspartic acid, glutamine or glutamic acid

<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  Xaa at position 10 is alanine or threonine

<220>
<221>  MISC_FEATURE
<222>  (17)..(17)
<223>  Xaa at position 12 is glutamic acid, aspartic acid or asparagine

<220>
<221>  MISC_FEATURE
<222>  (18)..(18)
<223>  Xaa at position 18 is alanine, ornithine, lysine or arginine

<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  Xaa at position 21 is tyrosine or 4-amino-phenylalanine

<400>  17

Xaa Leu Cys Gly Xaa Xaa Leu Val Xaa Xaa Leu Tyr Leu Val Cys Gly 
1               5                   10                  15      


Xaa Xaa Gly Phe Xaa 
            20      


<210>  18
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Analog of the insulin A chain


<220>
<221>  MISC_FEATURE
<222>  (4)..(4)
<223>  Xaa at position 5 is aspartic acid or glutamic acid

<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  Xaa at position 5 is glutamine or glutamic acid

<220>
<221>  MISC_FEATURE
<222>  (8)..(8)
<223>  Xaa at position 8 is histidine, threonine or phenylalanine

<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  Xaa at position 9 is serine, arginine, ornithine, lysine or 
       alanine

<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  Xaa at position 10 is isoleucine or serine

<220>
<221>  MISC_FEATURE
<222>  (12)..(12)
<223>  Xaa at position 12 is aspartic acid or serine

<220>
<221>  MISC_FEATURE
<222>  (14)..(14)
<223>  Xaa at position 14 is tyrosine, arginine, ornathine, lysine or 
       alanine

<220>
<221>  MISC_FEATURE
<222>  (15)..(15)
<223>  Xaa at position 15 is glutamine, glutamic acid, arginine, 
       ornithine, alanine, lysine or leucine

<220>
<221>  MISC_FEATURE
<222>  (17)..(17)
<223>  Xaa at position 17 is glutamine or glutamic acid

<220>
<221>  MISC_FEATURE
<222>  (18)..(18)
<223>  Xaa at position 18 is methionine, asparagine, glutamine, glutamic
       acid, aspartic acid or threonine

<220>
<221>  MISC_FEATURE
<222>  (19)..(19)
<223>  Xaa at position19 is tyrosine, 4-methoxy phenylalanine  or 
       4-amino-phenylalanine

<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  Xaa at position 21 is alanine, glycine, serine, valine, 
       threonine, isoleucine, leucine, glutamine, glutamic acid, 
       asparagine, aspartic acid, histidine, tryptophan, tyrosine, or 
       methionine

<400>  18

Gly Ile Val Xaa Xaa Cys Cys Xaa Xaa Xaa Cys Xaa Leu Xaa Xaa Leu 
1               5                   10                  15      


Xaa Xaa Xaa Cys Xaa 
            20      


<210>  19
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker peptide


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  the Xaa at position 1 is glycine, glutamic acid or aspartic acid

<220>
<221>  MISC_FEATURE
<222>  (2)..(6)
<223>  the Xaas at positions 2-6 are independently glutamic acid or 
       aspartic acid

<400>  19

Xaa Xaa Xaa Xaa Xaa Xaa Lys 
1               5           


<210>  20
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker peptide


<220>
<221>  MISC_FEATURE
<222>  (2)..(6)
<223>  the Xaas at positions 2-6 are independently glutamic acid or 
       aspartic acid

<400>  20

Gly Xaa Xaa Xaa Xaa Xaa Lys 
1               5           


<210>  21
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker


<220>
<221>  MISC_FEATURE
<222>  (1)..(5)
<223>  the Xaas at positions 1-5 are independently glutamic acid or 
       aspartic acid

<400>  21

Xaa Xaa Xaa Xaa Xaa Arg Lys 
1               5           


<210>  22
<211>  31
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  analog of IGF-1 B chain


<220>
<221>  MISC_FEATURE
<222>  (28)..(28)
<223>  The Xaa at position 28 is alanine lysine, ornithine or arginine

<400>  22

Gly Glu Glu Glu Glu Glu Lys Gly Pro Glu His Leu Cys Gly Ala His 
1               5                   10                  15      


Leu Val Asp Ala Leu Tyr Leu Val Cys Gly Asp Xaa Gly Phe Tyr 
            20                  25                  30      


<210>  23
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Analog of the insulin A chain


<220>
<221>  MISC_FEATURE
<222>  (8)..(8)
<223>  Xaa at position 8 is histidine or threonine

<220>
<221>  MISC_FEATURE
<222>  (17)..(17)
<223>  Xaa at position 17 is glutamine or glutamic acid

<220>
<221>  MISC_FEATURE
<222>  (19)..(19)
<223>  Xaa at position19 is tyrosine, 4-methoxy phenylalanine  or 
       4-amino-phenylalanine

<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  Xaa at position 21 is asparagine or glycine

<400>  23

Gly Ile Val Glu Gln Cys Cys Xaa Ser Ile Cys Ser Leu Tyr Gln Leu 
1               5                   10                  15      


Xaa Asn Xaa Cys Xaa 
            20      


<210>  24
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Analog of the insulin B chain


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  Xaa at position 1 is histidine or threonine

<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  Xaa at position 5 is alanine, glycine or serine

<220>
<221>  MISC_FEATURE
<222>  (6)..(6)
<223>  Xaa at position 6 is histidine, aspartic acid, glutamic acid, 
       homocysteic acid or cysteic acid

<400>  24

Xaa Leu Cys Gly Xaa Xaa Leu Val Glu Ala Leu Tyr Leu Val Cys Gly 
1               5                   10                  15      


Glu Arg Gly Phe Phe 
            20      


<210>  25
<211>  27
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Analog of the insulin B chain


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  Xaa at position 1 is phenylalanine and desamino-phenylalanine

<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  Xaa at position 5 is histidine and threonine

<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  Xaa at position 9 is alanine, glycine or serine

<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  Xaa at position 10 is histidine, aspartic acid, glutamic acid, 
       homocysteic acid or cysteic acid

<400>  25

Xaa Val Asn Gln Xaa Leu Cys Gly Xaa Xaa Leu Val Glu Ala Leu Tyr 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr 
            20                  25          


<210>  26
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Analog of the insulin A chain


<220>
<221>  MISC_FEATURE
<222>  (8)..(8)
<223>  Xaa at position 8 is histidine or phenylalanine

<220>
<221>  MISC_FEATURE
<222>  (19)..(19)
<223>  Xaa at position19 is tyrosine or 4-amino-phenylalanine

<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  Xaa at position 21 is alanine, glycine or asparagine

<400>  26

Gly Ile Val Glu Gln Cys Cys Xaa Ser Ile Cys Ser Leu Tyr Gln Leu 
1               5                   10                  15      


Glu Asn Xaa Cys Xaa 
            20      


<210>  27
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Analog of the insulin A chain


<220>
<221>  MISC_FEATURE
<222>  (8)..(8)
<223>  Xaa at position 8 is histidine or phenylalnine

<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  Xaa at position 9 is arginine, lysine, ornithine or alanine

<220>
<221>  MISC_FEATURE
<222>  (14)..(14)
<223>  Xaa at position 14 is arginine, lysine, ornithine or alanine

<220>
<221>  MISC_FEATURE
<222>  (15)..(15)
<223>  Xaa at position 15 is arginine, lysine, ornithine or leucine

<220>
<221>  MISC_FEATURE
<222>  (17)..(17)
<223>  Xaa at position 17 is glutamine or glutamic acid

<220>
<221>  MISC_FEATURE
<222>  (18)..(18)
<223>  Xaa at position 18 is methionine, asparagine or threonine

<220>
<221>  MISC_FEATURE
<222>  (19)..(19)
<223>  Xaa at position19 is tyrosine, 4-methoxy phenylalanine  or 
       4-amino-phenylalanine

<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  Xaa at position 21 is alanine, glycine or asparagine

<400>  27

Gly Ile Val Asp Glu Cys Cys Xaa Xaa Ser Cys Asp Leu Xaa Xaa Leu 
1               5                   10                  15      


Xaa Xaa Xaa Cys Xaa 
            20      


<210>  28
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Analog of the insulin B chain


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  Xaa at position 1 is histidine or threonine

<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  Xaa at position 5 is alanine, glycine or serine

<220>
<221>  MISC_FEATURE
<222>  (6)..(6)
<223>  Xaa at position 6 is histidine, aspartic acid, glutamic acid, 
       homocysteic acid or cysteic acid

<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  Xaa at position 9 is aspartic acid or glutamic acid

<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  Xaa at position 10 is alanine or threonine

<220>
<221>  MISC_FEATURE
<222>  (18)..(18)
<223>  Xaa at position 18 is alanine, ornithine, lysine or arginine

<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  Xaa at position 21 is tyrosine or phenylalanine

<400>  28

Xaa Leu Cys Gly Xaa Xaa Leu Val Xaa Xaa Leu Tyr Leu Val Cys Gly 
1               5                   10                  15      


Asp Xaa Gly Phe Xaa 
            20      


<210>  29
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Analog of the insulin A chain


<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  Xaa at position 9 is arginine, ornithine, or lysine

<220>
<221>  MISC_FEATURE
<222>  (14)..(14)
<223>  Xaa at position 14 is arginine, ornithine, or lysine

<220>
<221>  MISC_FEATURE
<222>  (15)..(15)
<223>  Xaa at position 15 is arginine, ornithine, or lysine

<220>
<221>  MISC_FEATURE
<222>  (17)..(17)
<223>  Xaa at position 17 is glutamine or glutamic acid

<220>
<221>  MISC_FEATURE
<222>  (19)..(19)
<223>  Xaa at position19 is tyrosine, 4-methoxy phenylalanine  or 
       4-amino-phenylalanine

<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  Xaa at position 21 is alanine, glycine or asparagine

<400>  29

Gly Ile Val Asp Glu Cys Cys His Xaa Ser Cys Asp Leu Xaa Xaa Leu 
1               5                   10                  15      


Xaa Met Xaa Cys Xaa 
            20      


<210>  30
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Analog of the insulin B chain


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  Xaa at position 1 is histidine or threonine

<220>
<221>  MISC_FEATURE
<222>  (6)..(6)
<223>  Xaa at position 6 is histidine, aspartic acid, or glutamic acid

<220>
<221>  MISC_FEATURE
<222>  (18)..(18)
<223>  Xaa at position 18 is alanine, ornithine, lysine or arginine

<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  Xaa at position 21 is tyrosine or phenylalanine

<400>  30

Xaa Leu Cys Gly Ala Xaa Leu Val Asp Ala Leu Tyr Leu Val Cys Gly 
1               5                   10                  15      


Asp Xaa Gly Phe Xaa 
            20      


<210>  31
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Analog of IGF-1 B chain


<220>
<221>  MISC_FEATURE
<222>  (18)..(18)
<223>  The Xaa at position 18 is ornithine, lysine or arginine

<400>  31

His Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Tyr Leu Val Cys Gly 
1               5                   10                  15      


Asp Xaa Gly Phe Tyr 
            20      


<210>  32
<211>  24
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Analog of IGF-1 B chain


<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  The Xaa at position 21 is ornithine, lysine or arginine

<400>  32

Gly Pro Glu His Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Tyr Leu 
1               5                   10                  15      


Val Cys Gly Asp Xaa Gly Phe Tyr 
            20                  


<210>  33
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Analog of IGF-1 B chain


<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  The Xaa at position 21 is ornithine, lysine or arginine

<400>  33

Gly Pro Glu His Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Tyr Leu 
1               5                   10                  15      


Val Cys Gly Asp Xaa Gly Phe Tyr Phe Asn Pro Lys Thr 
            20                  25                  


<210>  34
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Analog of IGF-1 B chain


<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  The Xaa at position 21 is ornithine, lysine or arginine

<400>  34

Gly Pro Glu His Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Tyr Leu 
1               5                   10                  15      


Val Cys Gly Asp Xaa Gly Phe Tyr Phe Asn Lys Pro Thr 
            20                  25                  


<210>  35
<211>  8
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (7)..(7)
<223>  Xaa at position 7 is ornithine

<400>  35

Gly Tyr Gly Ser Ser Ser Xaa Arg 
1               5               


<210>  36
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Analog of the insulin A chain


<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  Xaa at position 9 is arginine, ornithine, or lysine

<220>
<221>  MISC_FEATURE
<222>  (14)..(14)
<223>  Xaa at position 14 is arginine, ornithine, or lysine

<220>
<221>  MISC_FEATURE
<222>  (15)..(15)
<223>  Xaa at position 15 is arginine, ornithine, or lysine

<400>  36

Gly Ile Val Asp Glu Cys Cys His Xaa Ser Cys Asp Leu Xaa Xaa Leu 
1               5                   10                  15      


Gln Met Tyr Cys Asn 
            20      


<210>  37
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Analog of the insulin A chain


<220>
<221>  MISC_FEATURE
<222>  (19)..(19)
<223>  Xaa at position19 is tyrosine, 4-methoxy phenylalanine  or 
       4-amino-phenylalanine

<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  Xaa at position 21 is alanine, glycine or asparagine

<400>  37

Gly Ile Val Glu Gln Cys Cys His Ser Ile Cys Ser Leu Tyr Gln Leu 
1               5                   10                  15      


Glu Asn Xaa Cys Xaa 
            20      


<210>  38
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Analog of the insulin A chain


<220>
<221>  MISC_FEATURE
<222>  (8)..(8)
<223>  Xaa at position 8 is histidine or phenylalnine

<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  Xaa at position 9 is arginine, lysine, ornithine or alanine

<220>
<221>  MISC_FEATURE
<222>  (14)..(14)
<223>  Xaa at position 14 is arginine, lysine, ornithine or alanine

<220>
<221>  MISC_FEATURE
<222>  (15)..(15)
<223>  Xaa at position 15 is arginine, lysine, ornithine or leucine

<220>
<221>  MISC_FEATURE
<222>  (17)..(17)
<223>  Xaa at position 17 is glutamine or glutamic acid

<220>
<221>  MISC_FEATURE
<222>  (18)..(18)
<223>  Xaa at position 18 is methionine, asparagine or threonine

<220>
<221>  MISC_FEATURE
<222>  (19)..(19)
<223>  Xaa at position19 is tyrosine, 4-methoxy phenylalanine  or 
       4-amino-phenylalanine

<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  Xaa at position 21 is alanine, glycine or asparagine

<400>  38

Gly Ile Val Asp Glu Cys Cys Xaa Xaa Ser Cys Asp Leu Xaa Xaa Leu 
1               5                   10                  15      


Xaa Xaa Xaa Cys Xaa 
            20      


<210>  39
<211>  21
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (18)..(18)
<223>  The Xaa at position 18 is ornithine

<400>  39

His Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Tyr Leu Val Cys Gly 
1               5                   10                  15      


Asp Xaa Gly Phe Tyr 
            20      


<210>  40
<211>  24
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  The Xaa at position 21is ornithine

<400>  40

Gly Pro Glu His Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Tyr Leu 
1               5                   10                  15      


Val Cys Gly Asp Xaa Gly Phe Tyr 
            20                  


<210>  41
<211>  29
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  The Xaa at position 21is ornithine

<400>  41

Gly Pro Glu His Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Tyr Leu 
1               5                   10                  15      


Val Cys Gly Asp Xaa Gly Phe Tyr Phe Asn Pro Lys Thr 
            20                  25                  


<210>  42
<211>  29
<212>  PRT
<213>  Homo sapiens


<220>
<221>  misc_feature
<222>  (21)..(21)
<223>  Xaa can be any naturally occurring amino acid

<400>  42

Gly Pro Glu His Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Tyr Leu 
1               5                   10                  15      


Val Cys Gly Asp Xaa Gly Phe Tyr Phe Asn Lys Pro Thr 
            20                  25                  


<210>  43
<211>  21
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  The Xaa at position 9 is ornithine

<220>
<221>  MISC_FEATURE
<222>  (14)..(15)
<223>  The Xaas at positions 14 and 15 are both ornithine

<220>
<221>  MISC_FEATURE
<222>  (19)..(19)
<223>  The Xaa at position 19 is tyrosine, 4-methoxy-phenylalanine or 
       4-amino phenylalanine

<400>  43

Gly Ile Val Asp Glu Cys Cys His Xaa Ser Cys Asp Leu Xaa Xaa Leu 
1               5                   10                  15      


Gln Met Xaa Cys Asn 
            20      


<210>  44
<211>  5
<212>  PRT
<213>  Homo sapiens

<400>  44

Phe Asn Lys Pro Thr 
1               5   


<210>  45
<211>  4
<212>  PRT
<213>  Homo sapiens

<400>  45

Phe Asn Lys Pro 
1               


<210>  46
<211>  4
<212>  PRT
<213>  Homo sapiens

<400>  46

Tyr Thr Pro Lys 
1               


<210>  47
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Analog of IGF-1 B chain sequence fragment

<400>  47

Phe Asn Pro Lys 
1               


<210>  48
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Analog of insulin B chain sequence fragment

<400>  48

Tyr Thr Lys Pro Thr 
1               5   


<210>  49
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Analog of IGF-1 B chain sequence fragment

<400>  49

Phe Asn Pro Lys Thr 
1               5   


<210>  50
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker peptide


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  The Xaa at position 1 is phenylalanine or desamino-phenylalanine

<400>  50

Xaa Val Asn Gln Thr 
1               5   


<210>  51
<211>  21
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (19)..(19)
<223>  The Xaa at position 19 is tyrosine, 4-methoxy-phenylalanine or 
       4-amino phenylalanine

<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  The Xaa at position 21 is alanine, glycine or asparagine

<400>  51

Gly Ile Val Asp Glu Cys Cys His Arg Ser Cys Asp Leu Arg Arg Leu 
1               5                   10                  15      


Glu Met Xaa Cys Xaa 
            20      


<210>  52
<211>  29
<212>  PRT
<213>  Homo sapiens

<400>  52

Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Tyr Leu 
1               5                   10                  15      


Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Pro Lys Thr 
            20                  25                  


<210>  53
<211>  35
<212>  PRT
<213>  Homo sapiens

<400>  53

Arg Arg Glu Ala Glu Asp Leu Gln Val Gly Gln Val Glu Leu Gly Gly 
1               5                   10                  15      


Gly Pro Gly Ala Gly Ser Leu Gln Pro Leu Ala Leu Glu Gly Ser Leu 
            20                  25                  30          


Gln Lys Arg 
        35  


<210>  54
<211>  51
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (22)..(22)
<223>  The Xaa at position 22 is ornithine

<220>
<221>  MISC_FEATURE
<222>  (39)..(39)
<223>  The Xaa at position 39 is ornithine

<220>
<221>  MISC_FEATURE
<222>  (44)..(45)
<223>  The Xaa at positions 44-45 are ornithine

<400>  54

Cys Gly Pro Glu His Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Tyr 
1               5                   10                  15      


Leu Val Cys Gly Asp Xaa Gly Phe Tyr Phe Asn Lys Pro Thr Gly Ile 
            20                  25                  30          


Val Asp Glu Cys Cys Phe Xaa Ser Cys Asp Leu Xaa Xaa Leu Glu Asn 
        35                  40                  45              


Tyr Cys Asn 
    50      


<210>  55
<211>  21
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (4)..(4)
<223>  Xaa at position 5 is aspartic acid or glutamic acid

<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  Xaa at position 5 is glutamine or glutamic acid

<220>
<221>  MISC_FEATURE
<222>  (8)..(8)
<223>  Xaa at position 8 is histidine, threonine or phenylalanine

<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  Xaa at position 9 is serine, arginine, ornithine, lysine or 
       alanine

<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  Xaa at position 10 is isoleucine or serine

<220>
<221>  MISC_FEATURE
<222>  (12)..(12)
<223>  Xaa at position 12 is aspartic acid or serine

<220>
<221>  MISC_FEATURE
<222>  (14)..(14)
<223>  Xaa at position 14 is tyrosine, arginine, ornathine, lysine or 
       alanine

<220>
<221>  MISC_FEATURE
<222>  (15)..(15)
<223>  Xaa at position 15 is glutamine, glutamic acid, arginine, 
       ornithine, alanine, lysine or leucine

<220>
<221>  MISC_FEATURE
<222>  (18)..(18)
<223>  Xaa at position 18 is methionine, asparagine, glutamine, glutamic
       acid, aspartic acid or threonine

<220>
<221>  MISC_FEATURE
<222>  (19)..(19)
<223>  Xaa at position19 is tyrosine, 4-methoxy phenylalanine  or 
       4-amino-phenylalanine

<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  Xaa at position 21 is alanine, glycine, serine, valine, 
       threonine, isoleucine, leucine, glutamine, glutamic acid, 
       asparagine, aspartic acid, histidine, tryptophan, tyrosine, or 
       methionine

<400>  55

Gly Ile Val Xaa Xaa Cys Cys Xaa Xaa Xaa Cys Xaa Leu Xaa Xaa Leu 
1               5                   10                  15      


Glu Xaa Xaa Cys Xaa 
            20      


<210>  56
<211>  21
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (6)..(6)
<223>  The Xaa at position 6 is histidine, aspartic acid, glutamic acid,
       homocysteic acid or cysteic acid

<400>  56

His Leu Cys Gly Ser Xaa Leu Val Glu Ala Leu Tyr Leu Val Cys Gly 
1               5                   10                  15      


Glu Arg Gly Phe Phe 
            20      


<210>  57
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic peptide for testing cleavage of dipeptide prodrug 
       element

<400>  57

His Ser Arg Gly Thr Phe 
1               5       


<210>  58
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic peptide for testing cleavage of dipeptide prodrug 
       element


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at position 2 is Sarcosine

<400>  58

Lys Xaa His Ser Thr Gly Thr Phe 
1               5               


<210>  59
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  glucagon analogue


<220>
<221>  MOD_RES
<222>  (1)..(1)
<223>  Xaa at position 1 is d-histidine

<220>
<221>  MOD_RES
<222>  (2)..(2)
<223>  Xaa at position 2 is d-threonine

<220>
<221>  MOD_RES
<222>  (3)..(3)
<223>  Xaa at position 3 is d-arginine

<220>
<221>  MOD_RES
<222>  (5)..(5)
<223>  Xaa at position 5 is d-threonine

<220>
<221>  MOD_RES
<222>  (6)..(6)
<223>  Xaa at position 6 is d-phenylalanine

<400>  59

Xaa Xaa Xaa Gly Xaa Xaa 
1               5       


<210>  60
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  glucagon analogue


<220>
<221>  MOD_RES
<222>  (1)..(1)
<223>  Xaa at position 1 is d-lysine

<220>
<221>  MOD_RES
<222>  (2)..(2)
<223>  Xaa at position 2 is d-sarcosine

<220>
<221>  MOD_RES
<222>  (3)..(3)
<223>  Xaa at position 3 is d-histidine

<220>
<221>  MOD_RES
<222>  (4)..(4)
<223>  Xaa at position 4 is d-threonine

<220>
<221>  MOD_RES
<222>  (5)..(5)
<223>  Xaa at position 5 is d-arginine

<220>
<221>  MOD_RES
<222>  (7)..(7)
<223>  Xaa at position 7 is d-threonine

<220>
<221>  MOD_RES
<222>  (8)..(8)
<223>  Xaa at position 8 is d-phenylalanine

<400>  60

Xaa Xaa Xaa Xaa Xaa Gly Xaa Xaa 
1               5               


<210>  61
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic peptide for testing cleavage of dipeptide prodrug 
       element


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  The Xaa at position 1 is histidine, d-histidine or 
       N-methyl-histdine

<400>  61

Xaa Ser Arg Gly Thr Phe 
1               5       


<210>  62
<211>  29
<212>  PRT
<213>  Homo sapiens

<400>  62

Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe 
1               5                   10                  15      


Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr 
            20                  25                  


<210>  63
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Analog of the insulin B chain


<220>
<221>  MISC_FEATURE
<222>  (19)..(19)
<223>  Xaa at position 19 is tyrosine or 4-amino phenylanaline

<400>  63

Gly Ile Val Asp Glu Cys Cys His Arg Ser Cys Asp Leu Arg Arg Leu 
1               5                   10                  15      


Glu Met Xaa Cys Ala 
            20      


<210>  64
<211>  29
<212>  PRT
<213>  Homo sapiens

<400>  64

Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg 
1               5                   10                  15      


Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Arg 
            20                  25                  


<210>  65
<211>  28
<212>  PRT
<213>  Homo sapiens

<400>  65

Ser Ser Ser Ser Arg Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg 
1               5                   10                  15      


Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln 
            20                  25              


<210>  66
<211>  29
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  Xaa at position 5 is lysine or Arginine

<220>
<221>  MISC_FEATURE
<222>  (29)..(29)
<223>  Xaa at position 29 is lysine or Arginine

<400>  66

Ser Ser Ser Ser Xaa Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg 
1               5                   10                  15      


Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Xaa 
            20                  25                  


<210>  67
<211>  93
<212>  PRT
<213>  Homo sapiens

<400>  67

Met Gly Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro 
1               5                   10                  15      


Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Glu Glu 
            20                  25                  30          


Glu Glu Glu Lys Gly Pro Glu His Leu Cys Gly Ala His Leu Val Asp 
        35                  40                  45              


Ala Leu Tyr Leu Val Cys Gly Asp Arg Gly Phe Tyr Gly Tyr Gly Ser 
    50                  55                  60                  


Ser Ser Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys Cys His 
65                  70                  75                  80  


Arg Ser Cys Asp Leu Arg Arg Leu Glu Asn Tyr Cys Asn 
                85                  90              


<210>  68
<211>  81
<212>  PRT
<213>  Homo sapiens

<400>  68

Gly Glu Glu Glu Glu Glu Lys Gly Pro Glu His Leu Cys Gly Ala His 
1               5                   10                  15      


Leu Val Asp Ala Leu Tyr Leu Val Cys Gly Asp Arg Gly Phe Tyr Ser 
            20                  25                  30          


Ser Ser Ser Arg Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu 
        35                  40                  45              


Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Lys Gly Ile Val Asp 
    50                  55                  60                  


Glu Cys Cys His Arg Ser Cys Asp Leu Arg Arg Leu Glu Asn Tyr Cys 
65                  70                  75                  80  


Asn 
    


<210>  69
<211>  26
<212>  PRT
<213>  Homo sapiens

<400>  69

Pro Pro Arg Pro Pro Gln Ser Ala Ser Pro Pro Asp Leu Ser Pro Leu 
1               5                   10                  15      


Ser Gly Thr Pro Ser Arg Pro Ser Leu Ser 
            20                  25      


<210>  70
<211>  81
<212>  PRT
<213>  Homo sapiens

<400>  70

Gly Glu Glu Glu Glu Glu Lys Gly Pro Glu His Leu Cys Gly Ala His 
1               5                   10                  15      


Leu Val Asp Ala Leu Tyr Leu Val Cys Gly Asp Arg Gly Phe Tyr Ser 
            20                  25                  30          


Ser Ser Ser Arg Ala Ala Ala Ala Ser Leu Ala Ser Ala Ser Arg Leu 
        35                  40                  45              


Ala Gly Ala Ser Asp Thr Ala Ile Leu Ala Gln Lys Gly Ile Val Asp 
    50                  55                  60                  


Glu Cys Cys His Arg Ser Cys Asp Leu Arg Arg Leu Glu Asn Tyr Cys 
65                  70                  75                  80  


Asn 
    


<210>  71
<211>  87
<212>  PRT
<213>  Homo sapiens

<400>  71

Gly Glu Glu Glu Glu Glu Lys Gly Pro Glu His Leu Cys Gly Ala His 
1               5                   10                  15      


Leu Val Asp Ala Leu Tyr Leu Val Cys Gly Asp Arg Gly Phe Tyr Arg 
            20                  25                  30          


Arg Glu Ala Glu Asp Leu Gln Val Gly Gln Val Glu Leu Gly Gly Gly 
        35                  40                  45              


Pro Gly Ala Gly Ser Leu Gln Pro Leu Ala Leu Glu Gly Ser Leu Gln 
    50                  55                  60                  


Arg Lys Gly Ile Val Asp Glu Cys Cys His Arg Ser Cys Asp Leu Arg 
65                  70                  75                  80  


Arg Leu Glu Asn Tyr Cys Asn 
                85          


<210>  72
<211>  64
<212>  PRT
<213>  Homo sapiens

<400>  72

Gly Glu Glu Glu Glu Glu Lys Gly Pro Glu His Leu Cys Gly Ala His 
1               5                   10                  15      


Leu Val Asp Ala Leu Tyr Leu Val Cys Gly Asp Arg Gly Phe Tyr Gly 
            20                  25                  30          


Tyr Gly Ser Ser Ser Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu 
        35                  40                  45              


Cys Cys His Arg Ser Cys Asp Leu Arg Arg Leu Glu Asn Tyr Cys Asn 
    50                  55                  60                  


<210>  73
<211>  116
<212>  PRT
<213>  Homo sapiens

<400>  73

Gly Glu Glu Glu Glu Glu Lys Gly Pro Glu His Leu Cys Gly Ala His 
1               5                   10                  15      


Leu Val Asp Ala Leu Tyr Leu Val Cys Gly Asp Arg Gly Phe Tyr Ser 
            20                  25                  30          


Ser Ser Ser Arg Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu 
        35                  40                  45              


Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Lys Arg Arg Glu Ala 
    50                  55                  60                  


Glu Asp Leu Gln Val Gly Gln Val Glu Leu Gly Gly Gly Pro Gly Ala 
65                  70                  75                  80  


Gly Ser Leu Gln Pro Leu Ala Leu Glu Gly Ser Leu Gln Arg Lys Gly 
                85                  90                  95      


Ile Val Asp Glu Cys Cys His Arg Ser Cys Asp Leu Arg Arg Leu Glu 
            100                 105                 110         


Asn Tyr Cys Asn 
        115     


<210>  74
<211>  116
<212>  PRT
<213>  Homo sapiens

<400>  74

Gly Glu Glu Glu Glu Glu Lys Gly Pro Glu His Leu Cys Gly Ala His 
1               5                   10                  15      


Leu Val Asp Ala Leu Tyr Leu Val Cys Gly Asp Arg Gly Phe Tyr Arg 
            20                  25                  30          


Arg Glu Ala Glu Asp Leu Gln Val Gly Gln Val Glu Leu Gly Gly Gly 
        35                  40                  45              


Pro Gly Ala Gly Ser Leu Gln Pro Leu Ala Leu Glu Gly Ser Leu Gln 
    50                  55                  60                  


Arg Lys Ser Ser Ser Ser Arg Ala Pro Pro Pro Ser Leu Pro Ser Pro 
65                  70                  75                  80  


Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Lys Gly 
                85                  90                  95      


Ile Val Asp Glu Cys Cys His Arg Ser Cys Asp Leu Arg Arg Leu Glu 
            100                 105                 110         


Asn Tyr Cys Asn 
        115     


<210>  75
<211>  110
<212>  PRT
<213>  Homo sapiens

<400>  75

Gly Glu Glu Glu Glu Glu Lys Gly Pro Glu His Leu Cys Gly Ala His 
1               5                   10                  15      


Leu Val Asp Ala Leu Tyr Leu Val Cys Gly Asp Arg Gly Phe Tyr Ser 
            20                  25                  30          


Ser Ser Ser Arg Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu 
        35                  40                  45              


Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Lys Ser Ser Ser Ser 
    50                  55                  60                  


Arg Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro 
65                  70                  75                  80  


Ser Asp Thr Pro Ile Leu Pro Gln Lys Gly Ile Val Asp Glu Cys Cys 
                85                  90                  95      


His Arg Ser Cys Asp Leu Arg Arg Leu Glu Asn Tyr Cys Asn 
            100                 105                 110 


<210>  76
<211>  81
<212>  PRT
<213>  Homo sapiens

<400>  76

Gly Glu Glu Glu Glu Glu Lys Gly Pro Glu His Leu Cys Gly Ala His 
1               5                   10                  15      


Leu Val Asp Ala Leu Tyr Leu Val Cys Gly Asp Arg Gly Phe Tyr Leu 
            20                  25                  30          


Gln Val Gly Gln Val Glu Leu Gly Gly Gly Pro Gly Ala Gly Ser Leu 
        35                  40                  45              


Gln Pro Leu Ala Leu Glu Gly Ser Leu Gln Arg Lys Gly Ile Val Asp 
    50                  55                  60                  


Glu Cys Cys His Arg Ser Cys Asp Leu Arg Arg Leu Glu Asn Tyr Cys 
65                  70                  75                  80  


Asn 
    


<210>  77
<211>  80
<212>  PRT
<213>  Homo sapiens

<400>  77

Gly Glu Glu Glu Glu Glu Lys Gly Pro Glu His Leu Cys Gly Ala His 
1               5                   10                  15      


Leu Val Asp Ala Leu Tyr Leu Val Cys Gly Asp Arg Gly Phe Tyr Arg 
            20                  25                  30          


Arg Glu Ala Glu Asp Leu Gln Val Gly Gln Val Glu Leu Ser Leu Gln 
        35                  40                  45              


Pro Leu Ala Leu Glu Gly Ser Leu Gln Arg Lys Gly Ile Val Asp Glu 
    50                  55                  60                  


Cys Cys His Arg Ser Cys Asp Leu Arg Arg Leu Glu Asn Tyr Cys Asn 
65                  70                  75                  80  


<210>  78
<211>  80
<212>  PRT
<213>  Homo sapiens

<400>  78

Gly Glu Glu Glu Glu Glu Lys Gly Pro Glu His Leu Cys Gly Ala His 
1               5                   10                  15      


Leu Val Asp Ala Leu Tyr Leu Val Cys Gly Asp Arg Gly Phe Tyr Arg 
            20                  25                  30          


Arg Glu Ala Glu Asp Leu Gln Val Gly Gln Val Glu Leu Gly Gly Gly 
        35                  40                  45              


Pro Gly Ala Gly Ser Leu Gln Pro Leu Arg Lys Gly Ile Val Asp Glu 
    50                  55                  60                  


Cys Cys His Arg Ser Cys Asp Leu Arg Arg Leu Glu Asn Tyr Cys Asn 
65                  70                  75                  80  


<210>  79
<211>  29
<212>  PRT
<213>  Homo sapiens

<400>  79

Ser Ser Ser Ser Arg Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg 
1               5                   10                  15      


Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Lys 
            20                  25                  


<210>  80
<211>  81
<212>  PRT
<213>  Homo sapiens

<400>  80

Gly Glu Glu Glu Glu Glu Lys Gly Pro Glu His Leu Cys Gly Ala His 
1               5                   10                  15      


Leu Val Asp Ala Leu Tyr Leu Val Cys Gly Asp Arg Gly Phe Tyr Ala 
            20                  25                  30          


Ala Ala Ala Arg Ala Pro Pro Pro Ala Leu Pro Ala Pro Ala Arg Leu 
        35                  40                  45              


Pro Gly Pro Ala Asp Thr Pro Ile Leu Pro Gln Lys Gly Ile Val Asp 
    50                  55                  60                  


Glu Cys Cys His Arg Ser Cys Asp Leu Arg Arg Leu Glu Asn Tyr Cys 
65                  70                  75                  80  


Asn 
    


<210>  81
<211>  87
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin analog

<400>  81

Gly Glu Glu Glu Glu Glu Lys Phe Val Asn Gln His Leu Cys Gly Ser 
1               5                   10                  15      


His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly Phe Phe 
            20                  25                  30          


Tyr Thr Asp Arg Thr Ser Ser Ser Ser Arg Ala Pro Pro Pro Ser Leu 
        35                  40                  45              


Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro 
    50                  55                  60                  


Gln Arg Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser Leu Tyr 
65                  70                  75                  80  


Gln Leu Glu Asn Tyr Cys Asn 
                85          


<210>  82
<211>  109
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin analog

<400>  82

Ser Ser Ser Ser Arg Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg 
1               5                   10                  15      


Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Lys Phe Val Asn 
            20                  25                  30          


Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr Leu Val Cys 
        35                  40                  45              


Gly Glu Arg Gly Phe Phe Tyr Thr Asp Arg Thr Ser Ser Ser Ser Lys 
    50                  55                  60                  


Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser 
65                  70                  75                  80  


Asp Thr Pro Ile Leu Pro Gln Arg Gly Ile Val Glu Gln Cys Cys Thr 
                85                  90                  95      


Ser Ile Cys Ser Leu Tyr Gln Leu Glu Asn Tyr Cys Asn 
            100                 105                 


<210>  83
<211>  82
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin analog

<400>  83

Gly Glu Glu Glu Glu Glu Lys Phe Val Asn Gln His Leu Cys Gly Ser 
1               5                   10                  15      


His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly Phe Phe 
            20                  25                  30          


Ser Ser Ser Ser Arg Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg 
        35                  40                  45              


Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Arg Gly Ile Val 
    50                  55                  60                  


Glu Gln Cys Cys Thr Ser Ile Cys Ser Leu Tyr Gln Leu Glu Asn Tyr 
65                  70                  75                  80  


Cys Asn 
        


<210>  84
<211>  82
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin analog

<400>  84

Gly Glu Glu Glu Glu Glu Lys Phe Val Asn Gln His Leu Cys Gly Ser 
1               5                   10                  15      


His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly Phe Phe 
            20                  25                  30          


Ser Ser Ser Ser Arg Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg 
        35                  40                  45              


Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Lys Gly Ile Val 
    50                  55                  60                  


Glu Gln Cys Cys Thr Ser Ile Cys Ser Leu Tyr Gln Leu Glu Asn Tyr 
65                  70                  75                  80  


Cys Asn 
        


<210>  85
<211>  81
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin analog

<400>  85

Gly Glu Glu Glu Glu Glu Lys Gly Pro Glu His Leu Cys Gly Ser His 
1               5                   10                  15      


Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly Phe Phe Ser 
            20                  25                  30          


Ser Ser Ser Arg Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu 
        35                  40                  45              


Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Lys Gly Ile Val Glu 
    50                  55                  60                  


Gln Cys Cys Thr Ser Ile Cys Ser Leu Tyr Gln Leu Glu Asn Tyr Cys 
65                  70                  75                  80  


Asn 
    


<210>  86
<211>  70
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin analog

<400>  86

Gly Glu Glu Glu Glu Glu Lys Phe Val Asn Gln His Leu Cys Gly Ser 
1               5                   10                  15      


His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly Phe Phe 
            20                  25                  30          


Tyr Thr Asp Arg Thr Gly Tyr Gly Ser Ser Ser Arg Arg Ala Pro Gln 
        35                  40                  45              


Thr Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser Leu Tyr Gln 
    50                  55                  60                  


Leu Glu Asn Tyr Cys Asn 
65                  70  


<210>  87
<211>  70
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin analog

<400>  87

Gly Glu Glu Glu Glu Glu Lys Phe Val Asn Gln His Leu Cys Gly Ser 
1               5                   10                  15      


His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly Phe Phe 
            20                  25                  30          


Tyr Thr Asp Arg Thr Gly Ala Gly Ser Ser Ser Arg Arg Ala Pro Gln 
        35                  40                  45              


Thr Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser Leu Tyr Gln 
    50                  55                  60                  


Leu Glu Asn Tyr Cys Asn 
65                  70  


<210>  88
<211>  75
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin analog

<400>  88

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Ser Ser Ser Ser Arg Ala Pro 
            20                  25                  30          


Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr 
        35                  40                  45              


Pro Ile Leu Pro Gln Arg Gly Ile Val Glu Gln Cys Cys Thr Ser Ile 
    50                  55                  60                  


Cys Ser Leu Tyr Gln Leu Glu Asn Tyr Cys Asn 
65                  70                  75  


<210>  89
<211>  75
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin analog

<400>  89

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Ser Ser Ser Ser Arg Ala Pro 
            20                  25                  30          


Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr 
        35                  40                  45              


Pro Ile Leu Pro Gln Lys Gly Ile Val Glu Gln Cys Cys Thr Ser Ile 
    50                  55                  60                  


Cys Ser Leu Tyr Gln Leu Glu Asn Tyr Cys Asn 
65                  70                  75  


<210>  90
<211>  74
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin analog

<400>  90

Gly Pro Glu His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr Leu 
1               5                   10                  15      


Val Cys Gly Glu Arg Gly Phe Phe Ser Ser Ser Ser Arg Ala Pro Pro 
            20                  25                  30          


Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro 
        35                  40                  45              


Ile Leu Pro Gln Lys Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys 
    50                  55                  60                  


Ser Leu Tyr Gln Leu Glu Asn Tyr Cys Asn 
65                  70                  


<210>  91
<211>  110
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  single chain insulin analog

<400>  91

Met Gly Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro 
1               5                   10                  15      


Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Glu Glu 
            20                  25                  30          


Glu Glu Glu Arg Gly Pro Glu His Leu Cys Gly Ala His Leu Val Asp 
        35                  40                  45              


Ala Leu Tyr Leu Val Cys Gly Asp Arg Gly Phe Tyr Ser Ser Ser Ser 
    50                  55                  60                  


Arg Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro 
65                  70                  75                  80  


Ser Asp Thr Pro Ile Leu Pro Gln Lys Gly Ile Val Asp Glu Cys Cys 
                85                  90                  95      


His Arg Ser Cys Asp Leu Arg Arg Leu Glu Asn Tyr Cys Asn 
            100                 105                 110 


<210>  92
<211>  28
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  Xaa at position 5 is lysine or Arginine

<400>  92

Ser Ser Ser Ser Xaa Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg 
1               5                   10                  15      


Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln 
            20                  25              


<210>  93
<211>  30
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  Xaa at position 5 is lysine or Arginine

<220>
<221>  misc_feature
<222>  (7)..(7)
<223>  Xaa can be any naturally occurring amino acid

<400>  93

Met Gly Ser Ser Ser Ser Xaa Ala Pro Pro Pro Ser Leu Pro Ser Pro 
1               5                   10                  15      


Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln 
            20                  25                  30  


<210>  94
<211>  30
<212>  PRT
<213>  Homo sapiens

<400>  94

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Arg Thr 
            20                  25                  30  


<210>  95
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Analog of the insulin A chain


<220>
<221>  MISC_FEATURE
<222>  (19)..(19)
<223>  Xaa at position19 is tyrosine, 4-methoxy phenylalanine  or 
       4-amino-phenylalanine

<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  Xaa at position 21 is alanine, glycine or asparagine

<400>  95

Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser Leu Tyr Gln Leu 
1               5                   10                  15      


Glu Asn Xaa Cys Xaa 
            20      


<210>  96
<211>  70
<212>  PRT
<213>  Homo sapiens

<400>  96

Gly Glu Glu Glu Glu Glu Lys Phe Val Asn Gln His Leu Cys Gly Ser 
1               5                   10                  15      


His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly Phe Phe 
            20                  25                  30          


Tyr Thr Asp Arg Thr Gly Tyr Gly Ser Ser Ser Arg Arg Ala Pro Gln 
        35                  40                  45              


Thr Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser Leu Tyr Gln 
    50                  55                  60                  


Leu Glu Asn Tyr Cys Asn 
65                  70  


<210>  97
<211>  70
<212>  PRT
<213>  Homo sapiens

<400>  97

Gly Glu Glu Glu Glu Glu Lys Phe Val Asn Gln His Leu Cys Gly Ser 
1               5                   10                  15      


His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly Phe Phe 
            20                  25                  30          


Tyr Thr Asp Arg Thr Gly Ala Gly Ser Ser Ser Arg Arg Ala Pro Gln 
        35                  40                  45              


Thr Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser Leu Tyr Gln 
    50                  55                  60                  


Leu Glu Asn Tyr Cys Asn 
65                  70  


<210>  98
<211>  82
<212>  PRT
<213>  Homo sapiens

<400>  98

Gly Glu Glu Glu Glu Glu Lys Phe Val Asn Gln His Leu Cys Gly Ser 
1               5                   10                  15      


His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly Phe Phe 
            20                  25                  30          


Ser Ser Ser Ser Arg Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg 
        35                  40                  45              


Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Arg Gly Ile Val 
    50                  55                  60                  


Glu Gln Cys Cys Thr Ser Ile Cys Ser Leu Tyr Gln Leu Glu Asn Tyr 
65                  70                  75                  80  


Cys Asn 
        


<210>  99
<211>  82
<212>  PRT
<213>  Homo sapiens

<400>  99

Gly Glu Glu Glu Glu Glu Lys Phe Val Asn Gln His Leu Cys Gly Ser 
1               5                   10                  15      


His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly Phe Phe 
            20                  25                  30          


Ser Ser Ser Ser Arg Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg 
        35                  40                  45              


Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Lys Gly Ile Val 
    50                  55                  60                  


Glu Gln Cys Cys Thr Ser Ile Cys Ser Leu Tyr Gln Leu Glu Asn Tyr 
65                  70                  75                  80  


Cys Asn 
        


<210>  100
<211>  87
<212>  PRT
<213>  Homo sapiens

<400>  100

Gly Glu Glu Glu Glu Glu Lys Phe Val Asn Gln His Leu Cys Gly Ser 
1               5                   10                  15      


His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly Phe Phe 
            20                  25                  30          


Tyr Thr Asp Arg Thr Ser Ser Ser Ser Arg Ala Pro Pro Pro Ser Leu 
        35                  40                  45              


Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro 
    50                  55                  60                  


Gln Arg Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser Leu Tyr 
65                  70                  75                  80  


Gln Leu Glu Asn Tyr Cys Asn 
                85          


<210>  101
<211>  58
<212>  PRT
<213>  Homo sapiens

<400>  101

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Ser Ser Ser Ser Arg Ala Pro 
            20                  25                  30          


Pro Pro Ser Leu Pro Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys 
        35                  40                  45              


Ser Leu Tyr Gln Leu Glu Asn Tyr Cys Asn 
    50                  55              


<210>  102
<211>  58
<212>  PRT
<213>  Homo sapiens

<400>  102

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Ser Ser Ser Ser Arg Ala Pro 
            20                  25                  30          


Ile Leu Pro Gln Lys Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys 
        35                  40                  45              


Ser Leu Tyr Gln Leu Glu Asn Tyr Cys Asn 
    50                  55              


<210>  103
<211>  63
<212>  PRT
<213>  Homo sapiens

<400>  103

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Ser Ser Ser Ser Arg Ala Pro 
            20                  25                  30          


Pro Pro Ser Leu Pro Ile Leu Pro Gln Lys Gly Ile Val Glu Gln Cys 
        35                  40                  45              


Cys Thr Ser Ile Cys Ser Leu Tyr Gln Leu Glu Asn Tyr Cys Asn 
    50                  55                  60              


<210>  104
<211>  25
<212>  PRT
<213>  Homo sapiens

<400>  104

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe 
            20                  25  


