                         SEQUENCE LISTING

<110>  Protagonist Therapeutics, Inc.
       Bourne, Gregory Thomas
       Smythe, Mark Leslie
       Frederick, Brian T.
       Bhandari, Ashok
 
<120>  ANALOGUES OF HEPCIDIN MIMETICS WITH IMPROVED IN VIVO HALF LIVES

<130>  PRTH-022/01WO

<160>  41    

<170>  PatentIn version 3.5

<210>  1
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Hepcidin analogue peptide formula


<220>
<221>  MOD_RES
<222>  (1)..(1)
<223>  Xaa is Asp, isoGlu or Ida

<220>
<221>  MOD_RES
<222>  (4)..(4)
<223>  Xaa is Phe, Phe(4-F), Phe(4-CN), 4-BIP, Phe(4-OCH3), Tyr,  
       Phe(2,3-(OCH3)2), Phe(2,3-Cl2), or Dpa

<220>
<221>  MOD_RES
<222>  (6)..(6)
<223>  Xaa is Cys or Pen

<220>
<221>  MOD_RES
<222>  (7)..(7)
<223>  Xaa is any amino acid

<220>
<221>  misc_feature
<222>  (8)..(8)
<223>  Xaa can be any naturally occurring amino acid

<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  Xaa is Lys, Glu or absent

<400>  1

Xaa Thr His Xaa Pro Xaa Xaa Xaa Phe Xaa 
1               5                   10  


<210>  2
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Hepcidin analogue peptide formula


<220>
<221>  MOD_RES
<222>  (1)..(5)
<223>  Xaa is any amino acid

<220>
<221>  MOD_RES
<222>  (6)..(6)
<223>  Xaa is Cys or Pen

<220>
<221>  MOD_RES
<222>  (7)..(7)
<223>  Xaa is Lys or absent

<400>  2

Xaa Xaa Xaa Xaa Xaa Xaa Xaa 
1               5           


<210>  3
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Hepcidin analogue peptide formula


<220>
<221>  MOD_RES
<222>  (4)..(4)
<223>  Phe or Dpa

<220>
<221>  MOD_RES
<222>  (6)..(6)
<223>  Cys or Pen

<220>
<221>  MOD_RES
<222>  (7)..(7)
<223>  Ile or Lys

<220>
<221>  MOD_RES
<222>  (8)..(8)
<223>  Lys or Arg

<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  Lys, Glu or absent

<400>  3

Asp Thr His Xaa Pro Xaa Xaa Xaa Phe Xaa 
1               5                   10  


<210>  4
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Hepcidin analogue peptide formula


<220>
<221>  MOD_RES
<222>  (5)..(5)
<223>  Gly or Sar

<220>
<221>  MOD_RES
<222>  (6)..(6)
<223>  Cys or Pen

<220>
<221>  MOD_RES
<222>  (7)..(7)
<223>  Lys or absent

<400>  4

Pro Arg Ser Lys Xaa Xaa Xaa 
1               5           


<210>  5
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue

<400>  5

Asp Thr His Phe Pro Cys Ile Lys Phe Lys Pro Arg Ser Lys Gly Cys 
1               5                   10                  15      


Lys 
    


<210>  6
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue

<400>  6

Asp Thr His Phe Pro Cys Ile Lys Phe Glu Pro Arg Ser Lys Gly Cys 
1               5                   10                  15      


Lys 
    


<210>  7
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (8)..(8)
<223>  IsoGlu-Palm conjugated half-life extension moiety

<400>  7

Asp Thr His Phe Pro Cys Ile Lys Phe Glu Pro Arg Ser Lys Gly Cys 
1               5                   10                  15      


Lys 
    


<210>  8
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  IsoGlu-Palm conjugated half-life extension moiety

<400>  8

Asp Thr His Phe Pro Cys Ile Lys Phe Lys Pro Arg Ser Lys Gly Cys 
1               5                   10                  15      


Lys 
    


<210>  9
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (6)..(6)
<223>  Pen

<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  IsoGlu-Palm conjugated half-life extension moiety

<220>
<221>  MOD_RES
<222>  (16)..(16)
<223>  Pen

<400>  9

Asp Thr His Phe Pro Xaa Ile Lys Phe Lys Pro Arg Ser Lys Gly Xaa 
1               5                   10                  15      


Lys 
    


<210>  10
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (6)..(6)
<223>  Pen

<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  IsoGlu-Palm conjugated half-life extension moiety

<400>  10

Asp Thr His Phe Pro Xaa Ile Lys Phe Lys Pro Arg Ser Lys Gly Cys 
1               5                   10                  15      


Lys 
    


<210>  11
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  IsoGlu-Palm conjugated half-life extension moiety

<220>
<221>  MOD_RES
<222>  (16)..(16)
<223>  Pen

<400>  11

Asp Thr His Phe Pro Cys Ile Lys Phe Lys Pro Arg Ser Lys Gly Xaa 
1               5                   10                  15      


Lys 
    


<210>  12
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  IsoGlu-Palm conjugated half-life extension moiety

<220>
<221>  MOD_RES
<222>  (15)..(15)
<223>  Sar (sarcosine0

<400>  12

Asp Thr His Phe Pro Cys Ile Lys Phe Lys Pro Arg Ser Lys Xaa Cys 
1               5                   10                  15      


Lys 
    


<210>  13
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (4)..(4)
<223>  beta, beta diphenylalanine

<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  IsoGlu-Palm conjugated half-life extension moiety

<400>  13

Asp Thr His Xaa Pro Cys Ile Lys Phe Lys Pro Arg Ser Lys Gly Cys 
1               5                   10                  15      


Lys 
    


<210>  14
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (4)..(4)
<223>  beta, beta diphenylalanine

<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  IsoGlu-Palm conjugated half-life extension moiety

<220>
<221>  MOD_RES
<222>  (15)..(15)
<223>  Sar (sarcosine)

<400>  14

Asp Thr His Xaa Pro Cys Ile Lys Phe Lys Pro Arg Ser Lys Xaa Cys 
1               5                   10                  15      


Lys 
    


<210>  15
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  IsoGlu-Palm conjugated half-life extension moiety

<400>  15

Asp Thr His Phe Pro Cys Ile Lys Phe Lys Pro Arg Ser Lys Gly Cys 
1               5                   10                  15      


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

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  IsoGlu-Palm conjugated half-life extension moiety

<220>
<221>  MOD_RES
<222>  (15)..(15)
<223>  Sar (sarcosine0

<400>  16

Asp Thr His Phe Pro Cys Ile Lys Phe Lys Pro Arg Ser Lys Xaa Cys 
1               5                   10                  15      


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

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  IsoGlu-Palm conjugated half-life extension moiety

<400>  17

Asp Thr His Phe Pro Cys Lys Lys Phe Lys Pro Arg Ser Lys Gly Cys 
1               5                   10                  15      


Lys 
    


<210>  18
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  IsoGlu-Lauric acid conjugated half-life extension moiety

<400>  18

Asp Thr His Phe Pro Cys Ile Lys Phe Lys Pro Arg Ser Lys Gly Cys 
1               5                   10                  15      


Lys 
    


<210>  19
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  IsoGlu-Myristic acid conjugated half-life extension moiety

<400>  19

Asp Thr His Phe Pro Cys Ile Lys Phe Lys Pro Arg Ser Lys Gly Cys 
1               5                   10                  15      


Lys 
    


<210>  20
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  IsoGlu-Bioitin conjugated half-life extension moiety

<400>  20

Asp Thr His Phe Pro Cys Ile Lys Phe Lys Pro Arg Ser Lys Gly Cys 
1               5                   10                  15      


Lys 
    


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

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  IsoGlu-Isovaleric acid conjugated half-life extension moiety

<400>  21

Asp Thr His Phe Pro Cys Ile Lys Phe Lys Pro Arg Ser Lys Gly Cys 
1               5                   10                  15      


Lys 
    


<210>  22
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  PEG2-Palm conjugated half-life extension moiety

<400>  22

Asp Thr His Phe Pro Cys Ile Lys Phe Lys Pro Arg Ser Lys Gly Cys 
1               5                   10                  15      


Lys 
    


<210>  23
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  PEG11-Palm conjugated half-life extension moiety

<400>  23

Asp Thr His Phe Pro Cys Ile Lys Phe Lys Pro Arg Ser Lys Gly Cys 
1               5                   10                  15      


Lys 
    


<210>  24
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  PEG11-Lauric acid conjugated half-life extension moiety

<400>  24

Asp Thr His Phe Pro Cys Ile Lys Phe Lys Pro Arg Ser Lys Gly Cys 
1               5                   10                  15      


Lys 
    


<210>  25
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  PEG11-Myristic acid conjugated half-life extension moiety

<400>  25

Asp Thr His Phe Pro Cys Ile Lys Phe Lys Pro Arg Ser Lys Gly Cys 
1               5                   10                  15      


Lys 
    


<210>  26
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  Palm conjugated half-life extension moiety

<400>  26

Asp Thr His Phe Pro Cys Ile Lys Phe Lys Pro Arg Ser Lys Gly Cys 
1               5                   10                  15      


Lys 
    


<210>  27
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  PEG8 conjugated half-life extension moiety

<400>  27

Asp Thr His Phe Pro Cys Ile Lys Phe Lys Pro Arg Ser Lys Gly Cys 
1               5                   10                  15      


Lys 
    


<210>  28
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  Ahx-Palm conjugated half-life extension moiety

<400>  28

Asp Thr His Phe Pro Cys Ile Lys Phe Lys Pro Arg Ser Lys Gly Cys 
1               5                   10                  15      


Lys 
    


<210>  29
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (8)..(8)
<223>  Ahx-Palm conjugated half-life extension moiety

<220>
<221>  MOD_RES
<222>  (15)..(15)
<223>  Sar (sarcosine)

<400>  29

Asp Thr His Phe Pro Cys Ile Lys Phe Glu Pro Arg Ser Lys Xaa Cys 
1               5                   10                  15      


Lys 
    


<210>  30
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  Ahx-Palm conjugated half-life extension moiety

<220>
<221>  MOD_RES
<222>  (15)..(15)
<223>  Sar (sarcosine)

<400>  30

Asp Thr His Phe Pro Cys Ile Lys Phe Lys Pro Arg Ser Lys Xaa Cys 
1               5                   10                  15      


Lys 
    


<210>  31
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  Ac conjugated half-life extension moiety

<400>  31

Asp Thr His Phe Pro Cys Ile Lys Phe Lys Pro Arg Ser Lys Gly Cys 
1               5                   10                  15      


Lys 
    


<210>  32
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (8)..(8)
<223>  PEG11-Palm conjugated half-life extension moiety

<220>
<221>  MOD_RES
<222>  (15)..(15)
<223>  Sar (sarcosine)

<400>  32

Asp Thr His Phe Pro Cys Ile Lys Phe Glu Pro Arg Ser Lys Xaa Cys 
1               5                   10                  15      


Lys 
    


<210>  33
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  PEG11-Palm conjugated half-life extension moiety

<220>
<221>  MOD_RES
<222>  (15)..(15)
<223>  Sar (sarcosine)

<400>  33

Asp Thr His Phe Pro Cys Ile Lys Phe Lys Pro Arg Ser Lys Xaa Cys 
1               5                   10                  15      


Lys 
    


<210>  34
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (8)..(8)
<223>  isoGlu-Ahx-Palm conjugated half-life extension moiety

<220>
<221>  MOD_RES
<222>  (15)..(15)
<223>  Sar (sarcosine)

<400>  34

Asp Thr His Phe Pro Cys Ile Lys Phe Glu Pro Arg Ser Lys Xaa Cys 
1               5                   10                  15      


Lys 
    


<210>  35
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (8)..(8)
<223>  OEG-OEG-isoGlu-(C18-diacid) conjugated half-life extension moiety

<220>
<221>  MOD_RES
<222>  (15)..(15)
<223>  Sar (sarcosine)

<400>  35

Asp Thr His Phe Pro Cys Ile Lys Phe Glu Pro Arg Ser Lys Xaa Cys 
1               5                   10                  15      


Lys 
    


<210>  36
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  IsoGlu-Octanoic acid conjugated half-life extension moiety

<400>  36

Asp Thr His Phe Pro Cys Ile Arg Phe Lys 
1               5                   10  


<210>  37
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  IDA (Iminodiacetic acid)

<220>
<221>  MOD_RES
<222>  (11)..(11)
<223>  beta alanine with Peg2-Palm conjugated half-life extension moiety

<400>  37

Asp Thr His Phe Pro Cys Ile Lys Phe Xaa Xaa 
1               5                   10      


<210>  38
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized hepcidin analogue


<220>
<221>  MOD_RES
<222>  (10)..(10)
<223>  IDA (Iminodiacetic acid)

<220>
<221>  MOD_RES
<222>  (11)..(11)
<223>  beta alanine with Peg11-Palm conjugated half-life extension 
       moiety

<400>  38

Asp Thr His Phe Pro Cys Ile Lys Phe Xaa Xaa 
1               5                   10      


<210>  39
<211>  25
<212>  PRT
<213>  Homo sapiens

<400>  39

Asp Thr His Phe Pro Ile Cys Ile Phe Cys Cys Gly Cys Cys His Arg 
1               5                   10                  15      


Ser Lys Cys Gly Met Cys Cys Lys Thr 
            20                  25  


<210>  40
<211>  9
<212>  PRT
<213>  Homo sapiens

<400>  40

Asp Thr His Phe Pro Ile Cys Ile Phe 
1               5                   


<210>  41
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized retro inverse peptide with D amino acids


<220>
<221>  MOD_RES
<222>  (1)..(9)
<223>  All amino acids are D amino acids

<400>  41

Phe Ile Cys Ile Pro Phe His Thr Asp 
1               5                   


