                         SEQUENCE LISTING

<110>  DiMarchi, Richard
       Cheng, Shujiang
       Kou, Binbin
       Jie, Han
 
<120>  YL-BASED INSULIN ANALOGS FOR TREATMENT OF INSULIN-DEPENDENT 
       DIABETES

<130>  32993-216453


<150>  61/358,181
<151>  2010-06-24

<160>  91    

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


<210>  9
<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 or arginine

<400>  9

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


Asp Xaa Gly Phe Tyr 
            20      


<210>  10
<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>  (9)..(9)
<223>  Xaa at position 9 is arginine or alanine

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

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

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

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

<400>  10

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


Glu Xaa Tyr Cys Xaa 
            20      


<210>  11
<211>  29
<212>  PRT
<213>  Artificial sequence

<220>
<223>  The "YL" analog of the IGF-2 B chain

<400>  11

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>  12
<211>  32
<212>  PRT
<213>  Artificial sequence

<220>
<223>  The "YL" Analog of the IGF-2 B chain

<400>  12

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>  13
<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>  (9)..(9)
<223>  Xaa at position 9 is arginine, orinithine or alanine

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

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

<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 position 19 is phenylalanine or 4-amino-phenylalanine

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

<400>  13

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


Glu Xaa Xaa Cys Xaa 
            20      


<210>  14
<211>  6
<212>  PRT
<213>  Homo sapiens

<400>  14

Ala Tyr Arg Pro Ser Glu 
1               5       


<210>  15
<211>  23
<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, glutamic acid, 
       homocysteic acid or cysteic acid

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

<400>  15

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


Asp Xaa Gly Phe Tyr Phe Asn 
            20              


<210>  16
<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>  (9)..(9)
<223>  Xaa at position 9 is arginine or alanine

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

<400>  16

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


Glu Met Tyr Cys Xaa 
            20      


<210>  17
<211>  26
<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, glutamic acid, 
       homocysteic acid or cysteic acid

<400>  17

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


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


<210>  18
<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, glutamic acid, 
       homocysteic acid or cysteic acid

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

<400>  18

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


Asp Xaa Gly Phe Tyr 
            20      


<210>  19
<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 or phenylalanine

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

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

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

<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 position 19 is tyrosine, 4-methoxy-phenylalanine or 
       4-amino-phenylalanine

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

<400>  19

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


Glu Xaa Xaa Cys Xaa 
            20      


<210>  20
<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>  (12)..(12)
<223>  Xaa at position 12 is tyrosine or 4-amino-phenylalanine

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

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

<400>  20

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>  21
<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>  (9)..(9)
<223>  Xaa at position 9 is arginine or alanine

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

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

<400>  21

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


Glu Met Xaa Cys Xaa 
            20      


<210>  22
<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 position 19 is phenylalanine or 4-amino-phenylalanine

<400>  22

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


Glu Met Xaa Cys Ala 
            20      


<210>  23
<211>  26
<212>  PRT
<213>  Artificial sequence

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


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

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

<400>  23

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


Asp Arg Gly Phe Xaa Phe Asn Lys Pro Thr 
            20                  25      


<210>  24
<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 position 19 is phenylalanine or 4-amino-phenylalanine

<400>  24

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


Glu Met Xaa Cys Asn 
            20      


<210>  25
<211>  26
<212>  PRT
<213>  Artificial Sequence

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


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

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

<400>  25

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


Asp Ala Gly Phe Xaa Phe Asn Lys Pro Thr 
            20                  25      


<210>  26
<211>  24
<212>  PRT
<213>  Artificial Sequence

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


<220>
<221>  MISC_FEATURE
<222>  (4)..(4)
<223>  Xaa at position 4 is histidine or threonine

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

<400>  26

Gly Pro Glu Xaa 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>  27
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  27

Gly Gly Gly Pro Gly Lys Arg 
1               5           


<210>  28
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  28

Gly Ser Ser Ser Arg Arg Ala Pro 
1               5               


<210>  29
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  29

Gly Gly Gly Gly Gly Lys Arg 
1               5           


<210>  30
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  30

Arg Arg Gly Gly Gly Gly Gly 
1               5           


<210>  31
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  31

Gly Gly Ala Pro Gly Asp Val Lys Arg 
1               5                   


<210>  32
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  32

Arg Arg Ala Pro Gly Asp Val Gly Gly 
1               5                   


<210>  33
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  33

Gly Gly Tyr Pro Gly Asp Val Lys Arg 
1               5                   


<210>  34
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  34

Arg Arg Tyr Pro Gly Asp Val Gly Gly 
1               5                   


<210>  35
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  35

Gly Gly His Pro Gly Asp Val Lys Arg 
1               5                   


<210>  36
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  36

Arg Arg His Pro Gly Asp Val Gly Gly 
1               5                   


<210>  37
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  37

Arg Arg Gly Pro Gly Gly Gly 
1               5           


<210>  38
<211>  59
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  single chain human insulin analog


<220>
<221>  MISC_FEATURE
<222>  (57)..(57)
<223>  Xaa at position 57 is a modified 4-amino phenylalanine

<400>  38

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


Asp Ala Gly Phe Tyr Phe Asp Leu Pro Thr Gln Pro Leu Ala Leu Glu 
            20                  25                  30          


Gly Ser Leu Gln Lys Arg Gly Ile Val Asp Glu Cys Cys His Ala Ser 
        35                  40                  45              


Cys Asp Leu Arg Arg Leu Glu Met Xaa Cys Asn 
    50                  55                  


<210>  39
<211>  59
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  single chain human insulin analog


<220>
<221>  MISC_FEATURE
<222>  (57)..(57)
<223>  Xaa at position 57 is modified 4-amino phenylalanine

<400>  39

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


Asp Arg Gly Phe Tyr Phe Asp Leu Pro Thr Gln Pro Leu Ala Leu Glu 
            20                  25                  30          


Gly Ser Leu Gln Lys Arg Gly Ile Val Asp Glu Cys Cys Phe Arg Ser 
        35                  40                  45              


Cys Asp Leu Arg Arg Leu Glu Met Xaa Cys Ala 
    50                  55                  


<210>  40
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  40

Ala Gly Arg Gly Ser Gly Lys 
1               5           


<210>  41
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  41

Ala Gly Leu Gly Ser Gly Lys 
1               5           


<210>  42
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  42

Ala Gly Met Gly Ser Gly Lys 
1               5           


<210>  43
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  43

Ala Ser Trp Gly Ser Gly Lys 
1               5           


<210>  44
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  44

Thr Gly Leu Gly Ser Gly Gln 
1               5           


<210>  45
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  45

Thr Gly Leu Gly Arg Gly Lys 
1               5           


<210>  46
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  46

Thr Gly Leu Gly Ser Gly Lys 
1               5           


<210>  47
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  47

His Gly Leu Tyr Ser Gly Lys 
1               5           


<210>  48
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  48

Lys Gly Leu Gly Ser Gly Gln 
1               5           


<210>  49
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  49

Val Gly Leu Met Ser Gly Lys 
1               5           


<210>  50
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  50

Val Gly Leu Ser Ser Gly Gln 
1               5           


<210>  51
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  51

Val Gly Leu Tyr Ser Gly Lys 
1               5           


<210>  52
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  52

Val Gly Leu Ser Ser Gly Lys 
1               5           


<210>  53
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  53

Val Gly Met Ser Ser Gly Lys 
1               5           


<210>  54
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  54

Val Trp Ser Ser Ser Gly Lys 
1               5           


<210>  55
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  55

Val Gly Ser Ser Ser Gly Lys 
1               5           


<210>  56
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  56

Val Gly Met Ser Ser Gly Lys 
1               5           


<210>  57
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  57

Thr Gly Leu Gly Ser Gly Arg 
1               5           


<210>  58
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  58

Thr Gly Leu Gly Lys Gly Gln 
1               5           


<210>  59
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  59

Lys Gly Leu Ser Ser Gly Gln 
1               5           


<210>  60
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  60

Val Lys Leu Ser Ser Gly Gln 
1               5           


<210>  61
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  61

Val Lys Leu Ser Ser Gly Gln 
1               5           


<210>  62
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  62

Thr Gly Leu Gly Lys Gly Gln 
1               5           


<210>  63
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  63

Val Gly Leu Ser Lys Gly Gln 
1               5           


<210>  64
<211>  26
<212>  PRT
<213>  Homo sapiens

<400>  64

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


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


<210>  65
<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>  (10)..(10)
<223>  Xaa at position 10 is alanine or threonine

<220>
<221>  misc_feature
<222>  (18)..(18)
<223>  Xaa at position 19 is alanine, arginine or ornithine


<400>  65

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


Asp Xaa Gly Phe Tyr 
            20      


<210>  66
<211>  94
<212>  PRT
<213>  Homo sapiens

<400>  66

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 Arg Arg 
            20                  25                  30          


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


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


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


Leu Glu Asn Tyr Cys Asn Pro Leu Lys Pro Ala Lys Ser Ala 
                85                  90                  


<210>  67
<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>  (17)..(17)
<223>  Xaa at position 17 is glutamic acid or aspartic acid

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

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

<400>  67

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>  68
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  68

Phe Gly Pro Glu 
1               


<210>  69
<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>  (9)..(9)
<223>  Xaa at position 9 is arginine or alanine

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

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

<400>  69

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


Glu Met Xaa Cys Xaa 
            20      


<210>  70
<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 position 19 is tyrosine, 4-amino phenylalanine

<400>  70

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


Glu Met Xaa Cys Ala 
            20      


<210>  71
<211>  30
<212>  PRT
<213>  Homo sapiens


<400>  71

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


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


<210>  72
<211>  30
<212>  PRT
<213>  Homo sapiens

<400>  72

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


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


<210>  73
<211>  6
<212>  PRT
<213>  Artificial Sequence

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

<400>  73

His Ser Arg Gly Thr Phe 
1               5       


<210>  74
<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>  74

Lys Xaa His Ser Thr Gly Thr Phe 
1               5               


<210>  75
<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>  75

Xaa Xaa Xaa Gly Xaa Xaa 
1               5       


<210>  76
<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>  d-phenylalanine

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

<400>  76

Xaa Xaa Xaa Xaa Xaa Gly Xaa Xaa 
1               5               


<210>  77
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Model hexapeptide for dipeptide cleavage experiments

<400>  77

His Ser Arg Gly Thr Phe 
1               5       


<210>  78
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  glucagon analogue


<220>
<221>  MOD_RES
<222>  (2)..(2)
<223>  dipeptide modified 4-amino-phenylalanine

<400>  78

His Xaa His Ser Arg Gly Thr Phe 
1               5               


<210>  79
<211>  12
<212>  PRT
<213>  Homo sapiens

<400>  79

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


<210>  80
<211>  8
<212>  PRT
<213>  Homo sapiens

<400>  80

Ser Arg Val Ser Arg Arg Ser Arg 
1               5               


<210>  81
<211>  8
<212>  PRT
<213>  Homo sapiens

<400>  81

Gly Ser Ser Ser Arg Arg Ala Pro 
1               5               


<210>  82
<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>  (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, ornithine, arginine or alanine

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

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

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

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

<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 position 19 is tyrosine, 4-methoxy-phenylalanine or 
       4-amino-phenylalanine

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

<400>  82

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>  83
<211>  48
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  IGF1 B and A chain analogs


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

<220>
<221>  MISC_FEATURE
<222>  (36)..(36)
<223>  Xaa at position 36 is ornithine

<220>
<221>  MISC_FEATURE
<222>  (41)..(41)
<223>  Xaa at position 41 is ornithine

<220>
<221>  MISC_FEATURE
<222>  (42)..(42)
<223>  Xaa at position 42 is ornithine

<400>  83

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 Gly Ile Val Asp Glu 
            20                  25                  30          


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


<210>  84
<211>  32
<212>  PRT
<213>  Homo sapiens


<400>  84

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


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

 
<210>  85
<211>  8
<212>  PRT
<213>  Homo sapiens


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

<400>  85

Gly Tyr Gly Ser Ser Ser Xaa Arg 
1               5               



<210>  86
<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>  (9)..(9)
<223>  Xaa at position 9 is arginine or alanine

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


<400>  86

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


Glu Met Xaa Cys Ala
            20      


<210>  87
<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 or phenylalanine

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

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

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

<400>  87

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


Glu Met Xaa Cys Xaa 
            20      


<210>  88
<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 or arginine

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

<400>  88

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>  89
<211>  12
<212>  PRT
<213>  Homo sapiens

<400>  89

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


<210>  90
<211>  8
<212>  PRT
<213>  Homo sapiens

<400>  90

Gly Tyr Gly Ser Ser Ser Arg Arg 
1               5               


<210>  91
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker sequence

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

<220>
<221>  MISC_FEATURE
<222>  (8)..(8)
<223>  Xaa at position 8 is Lysine, ornithine or arginine


<400>  91

Gly Tyr Gly Ser Ser Ser Xaa Xaa  
1               5                   
