                         SEQUENCE LISTING

<110>  Acworth Pharmaceuticals, Inc.
       LEONARD, Jack L.
 
<120>  Peptide Mimetics of DKK3b and Methods of Use

<130>  4261.3000 WO

<140>  PCT/US20/57841
<141>  2020-10-29

<150>  62/927,328
<151>  2019-10-29

<160>  81    

<170>  PatentIn version 3.5

<210>  1
<211>  98
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  AC1

<400>  1

Met Asp Ala Glu Asp Leu Leu Leu Lys Leu Asn Leu Ala Ala Thr Val 
1               5                   10                  15      


Gly Thr Ala Pro Pro Lys Gly Lys Asn Leu Gly Gln Ala Tyr Pro Ala 
            20                  25                  30          


Ser Ser Asp Lys Glu Ser Glu Val Gly Arg Tyr Ser His Ser Pro His 
        35                  40                  45              


Gln Gly Ser Ser Ala Cys Met Val Ala Arg Arg Arg Arg Arg Arg Ala 
    50                  55                  60                  


His Arg Asp Gly Met Ala Cys Pro Ser Thr Arg Ser Asn Asn Gly Ile 
65                  70                  75                  80  


Ala Ile Pro Val Pro Thr Ala Ala Leu Leu Ile Ile Leu Gly Gly Asp 
                85                  90                  95      


Asp Ile 
        


<210>  2
<211>  325
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  cpDKK3b fusion protein

<400>  2

Met Arg Gly Ser Leu Lys His His His His His His Leu Lys Gly Met 
1               5                   10                  15      


Ala Ser Met Thr Gly Gly Gln Gln Met Lys Leu Gly Asp Ile Tyr Ala 
            20                  25                  30          


Arg Ala Ala Ala Arg Gln Ala Arg Ala Asp Ile Gly Gly Ser Thr Met 
        35                  40                  45              


Glu Ala Glu Glu Ala Ala Ala Lys Ala Ser Ser Glu Val Asn Leu Ala 
    50                  55                  60                  


Asn Leu Pro Pro Ser Tyr His Asn Glu Thr Asn Thr Asp Thr Lys Val 
65                  70                  75                  80  


Gly Asn Asn Thr Ile His Val His Arg Glu Ile His Lys Ile Thr Asn 
                85                  90                  95      


Asn Gln Thr Gly Met Val Phe Ser Glu Thr Val Ile Thr Ser Val Gly 
            100                 105                 110         


Asp Glu Glu Gly Arg Arg Ser His Glu Cys Ile Ile Asp Glu Asp Cys 
        115                 120                 125             


Gly Pro Ser Met Tyr Cys Gln Phe Ala Ser Phe Gln Tyr Thr Cys Gln 
    130                 135                 140                 


Pro Cys Arg Gly Gln Arg Met Leu Cys Thr Arg Asp Ser Glu Cys Cys 
145                 150                 155                 160 


Gly Asp Gln Leu Cys Val Trp Gly His Cys Thr Lys Met Ala Thr Arg 
                165                 170                 175     


Gly Ser Asn Gly Thr Ile Cys Asp Asn Gln Arg Asp Cys Gln Pro Gly 
            180                 185                 190         


Leu Cys Cys Ala Phe Gln Arg Gly Leu Leu Phe Pro Val Cys Thr Pro 
        195                 200                 205             


Leu Pro Val Glu Gly Glu Leu Cys His Asp Pro Ala Ser Arg Leu Leu 
    210                 215                 220                 


Asp Leu Ile Thr Trp Glu Leu Glu Pro Asp Gly Ala Leu Asp Arg Cys 
225                 230                 235                 240 


Pro Cys Ala Ser Gly Leu Leu Cys Gln Pro His Ser His Ser Leu Val 
                245                 250                 255     


Tyr Val Cys Lys Pro Thr Phe Val Gly Ser Arg Asp Gln Asp Gly Glu 
            260                 265                 270         


Ile Leu Leu Pro Arg Glu Val Pro Asp Glu Tyr Glu Val Gly Ser Phe 
        275                 280                 285             


Met Glu Glu Val Arg Gln Glu Leu Glu Asp Leu Glu Arg Ser Leu Thr 
    290                 295                 300                 


Glu Glu Met Ala Leu Arg Glu Pro Ala Ala Ala Ala Ala Ala Leu Leu 
305                 310                 315                 320 


Gly Gly Glu Glu Ile 
                325 


<210>  3
<211>  67
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DKK1 Residues 74-141

<400>  3

Gln Thr Ile Asp Asn Tyr Gln Pro Tyr Pro Cys Ala Glu Asp Glu Glu 
1               5                   10                  15      


Cys Gly Thr Asp Glu Tyr Cys Ala Ser Pro Thr Arg Gly Gly Asp Ala 
            20                  25                  30          


Gly Val Gln Ile Cys Leu Ala Cys Arg Lys Arg Arg Lys Arg Cys Met 
        35                  40                  45              


Arg His Ala Met Cys Cys Pro Gly Asn Tyr Cys Lys Asn Gly Ile Cys 
    50                  55                  60                  


Val Ser Ser 
65          


<210>  4
<211>  53
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DKK2 Residues 78-130

<400>  4

Cys Ser Ser Asp Lys Glu Cys Glu Val Gly Arg Tyr Cys His Ser Pro 
1               5                   10                  15      


His Gln Gly Ser Ser Ala Cys Met Val Cys Arg Arg Lys Lys Lys Arg 
            20                  25                  30          


Cys His Arg Asp Gly Met Cys Cys Pro Ser Thr Arg Cys Asn Asn Gly 
        35                  40                  45              


Ile Cys Ile Pro Val 
    50              


<210>  5
<211>  53
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DKK3b Residues 74-126

<400>  5

His Glu Cys Ile Ile Asp Glu Asp Cys Gly Pro Ser Met Tyr Cys Gln 
1               5                   10                  15      


Phe Ala Ser Phe Gln Tyr Thr Cys Gln Pro Cys Arg Gly Gln Arg Met 
            20                  25                  30          


Leu Cys Thr Arg Asp Ser Glu Cys Cys Gly Asp Gln Leu Cys Val Trp 
        35                  40                  45              


Gly His Cys Thr Lys 
    50              


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

<220>
<223>  DKK4 Residues 31-91

<400>  6

Asp Leu His Gly Ala Arg Lys Gly Ser Gln Cys Leu Ser Asp Thr Asp 
1               5                   10                  15      


Cys Asn Thr Arg Lys Phe Cys Leu Gln Pro Arg Asp Glu Lys Pro Phe 
            20                  25                  30          


Cys Ala Thr Cys Arg Gly Leu Arg Arg Arg Cys Gln Arg Asp Ala Met 
        35                  40                  45              


Cys Cys Pro Gly Thr Leu Cys Val Asn Asp Val Cys Thr 
    50                  55                  60      


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

<220>
<223>  Cysteine deficient DKK3b OR Modified DKK3b

<400>  7

His Glu Ala Ile Ile Asp Glu Asp Ser Gly Pro Ser Met Tyr Ser Gln 
1               5                   10                  15      


Phe Ala Ser Phe Gln Tyr Thr Cys Gln Pro Ala Arg Arg Arg Arg Arg 
            20                  25                  30          


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


Gly His Ser Thr Lys 
    50              


<210>  8
<211>  67
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Cysteine deficient DKK1 OR Modified DKK1

<400>  8

Gln Thr Ile Asp Asn Tyr Gln Pro Tyr Pro Ala Ala Glu Asp Glu Glu 
1               5                   10                  15      


Ser Gly Thr Asp Glu Tyr Ser Ala Ser Pro Thr Arg Gly Gly Asp Ala 
            20                  25                  30          


Gly Val Gln Ile Cys Leu Ala Ala Arg Arg Arg Arg Arg Arg Ala Met 
        35                  40                  45              


Arg His Ala Met Ser Cys Pro Gly Asn Tyr Ala Lys Asn Gly Ile Ala 
    50                  55                  60                  


Val Ser Ser 
65          


<210>  9
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C. elegans SDC3

<400>  9

Phe Lys Lys Phe Arg Lys Phe 
1               5           


<210>  10
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CADY-K

<400>  10

Gly Leu Trp Arg Ala Leu Trp Arg Leu Leu Arg Ser Leu Trp Arg Leu 
1               5                   10                  15      


Leu Trp Lys 
            


<210>  11
<211>  23
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  EB1 CPP

<400>  11

Leu Ile Arg Leu Trp Ser His Leu Ile His Ile Trp Phe Gln Asn Arg 
1               5                   10                  15      


Arg Leu Lys Trp Lys Lys Lys 
            20              


<210>  12
<211>  27
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FBP CPP

<400>  12

Gly Ala Leu Phe Leu Gly Trp Leu Gly Ala Ala Gly Ser Thr Met Gly 
1               5                   10                  15      


Ala Trp Ser Gln Pro Lys Lys Lys Arg Lys Val 
            20                  25          


<210>  13
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FGF4 CPP

<400>  13

Ala Ala Val Ala Leu Leu Pro Ala Val Leu Leu Ala Leu Leu Ala Pro 
1               5                   10                  15      


<210>  14
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  HATF3

<400>  14

Glu Arg Lys Lys Arg Arg Arg Glu 
1               5               


<210>  15
<211>  22
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hCT CPP

<400>  15

Leu Gly Thr Tyr Thr Gln Asp Phe Asn Lys Thr Phe Pro Gln Thr Ala 
1               5                   10                  15      


Ile Gly Val Gly Ala Pro 
            20          


<210>  16
<211>  18
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  MAP CPP

<400>  16

Lys Leu Ala Leu Lys Leu Ala Leu Lys Ala Leu Lys Ala Ala Leu Lys 
1               5                   10                  15      


Leu Ala 
        


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

<220>
<223>  MPG CPP

<400>  17

Gly Leu Ala Phe Leu Gly Phe Leu Gly Ala Ala Gly Ser Thr Met Gly 
1               5                   10                  15      


Ala Trp Ser Gln Pro Lys Lys Lys Arg Lys Val 
            20                  25          


<210>  18
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  NF-kB

<400>  18

Val Gln Arg Lys Arg Gln Lys Leu Met Pro 
1               5                   10  


<210>  19
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  OCT-6

<400>  19

Gly Arg Lys Arg Lys Lys Arg Thr 
1               5               


<210>  20
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Penetratin CPP

<400>  20

Arg Gln Ile Lys Ile Trp Phe Gln Asn Arg Arg Met Lys Trp Lys Lys 
1               5                   10                  15      


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

<220>
<223>  Penetratin CPP variant 1

<400>  21

Arg Gln Leu Lys Leu Trp Phe Gln Asn Arg Arg Met Lys Trp Lys Lys 
1               5                   10                  15      


<210>  22
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Penetratin CPP variant 2

<400>  22

Arg Glu Ile Lys Ile Trp Phe Gln Asn Arg Arg Met Lys Trp Lys Lys 
1               5                   10                  15      


<210>  23
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Pep-1 CPP

<400>  23

Lys Glu Thr Trp Trp Glu Thr Trp Trp Thr Glu Trp Ser Gln Pro Lys 
1               5                   10                  15      


Lys Arg Lys Val 
            20  


<210>  24
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  pIsl CPP

<400>  24

Pro Val Ile Arg Val Trp Phe Gln Asn Lys Arg Cys Lys Asp Lys Lys 
1               5                   10                  15      


<210>  25
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Poly-Arg CPP


<220>
<221>  MISC_FEATURE
<222>  (5)..(10)
<223>  Xaa at positions 5-10 are Arg and up to six of them may be absent

<400>  25

Arg Arg Arg Arg Xaa Xaa Xaa Xaa Xaa Xaa 
1               5                   10  


<210>  26
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  pVEC CPP

<400>  26

Leu Leu Ile Ile Leu Arg Arg Arg Ile Arg Lys Gln Ala His Ala His 
1               5                   10                  15      


<210>  27
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  RL-16 CPP

<400>  27

Arg Arg Leu Arg Arg Leu Leu Arg Arg Leu Leu Arg Arg Leu Arg Arg 
1               5                   10                  15      


<210>  28
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  RVG CPP

<400>  28

Arg Val Gly Arg Arg Arg Arg Arg Arg Arg Arg Arg 
1               5                   10          


<210>  29
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  R6W3 CPP

<400>  29

Arg Arg Trp Trp Arg Arg Trp Arg Arg 
1               5                   


<210>  30
<211>  27
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  SBP CPP

<400>  30

Met Gly Leu Gly Leu His Leu Leu Val Leu Ala Ala Ala Leu Gln Gly 
1               5                   10                  15      


Ala Trp Ser Gln Pro Lys Lys Lys Arg Lys Val 
            20                  25          


<210>  31
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  SV40

<400>  31

Pro Lys Lys Lys Arg Lys Val 
1               5           


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

<220>
<223>  SynB1 CPP

<400>  32

Arg Gly Gly Arg Leu Ser Tyr Ser Arg Arg Phe Ser Thr Ser Thr Gly 
1               5                   10                  15      


Arg 
    


<210>  33
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  SynB3 CPP

<400>  33

Arg Arg Leu Ser Tyr Ser Arg Arg Arg Phe 
1               5                   10  


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

<220>
<223>  SynB5 CPP

<400>  34

Arg Gly Gly Arg Leu Ala Tyr Leu Arg Arg Arg Trp Ala Val Leu Gly 
1               5                   10                  15      


Arg 
    


<210>  35
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Tat47-57 CPP

<400>  35

Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg 
1               5                   10      


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

<220>
<223>  Tat47-56 CPP

<400>  36

Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg 
1               5                   10  


<210>  37
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Tat48-56 CPP

<400>  37

Gly Arg Lys Lys Arg Arg Gln Arg Arg 
1               5                   


<210>  38
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Tat48-60 CPP

<400>  38

Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg Pro Pro Gln 
1               5                   10              


<210>  39
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TCF1-a

<400>  39

Gly Lys Lys Lys Lys Arg Lys Arg Glu Lys Leu 
1               5                   10      


<210>  40
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TFIIE-b

<400>  40

Ser Lys Lys Lys Lys Thr Lys Val 
1               5               


<210>  41
<211>  27
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TP CPP

<400>  41

Gly Trp Thr Leu Asn Ser Ala Gly Tyr Leu Leu Gly Lys Ile Asn Leu 
1               5                   10                  15      


Lys Ala Leu Ala Ala Leu Ala Lys Lys Ile Leu 
            20                  25          


<210>  42
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TP10 CPP

<400>  42

Ala Gly Tyr Leu Leu Gly Lys Ile Asn Leu Lys Ala Leu Ala Ala Leu 
1               5                   10                  15      


Ala Lys Lys Ile Leu 
            20      


<210>  43
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TP2 CPP

<400>  43

Pro Leu Ile Tyr Leu Arg Leu Leu Arg Gly Gln Phe 
1               5                   10          


<210>  44
<211>  34
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VP22 CPP

<400>  44

Asp Ala Ala Thr Ala Thr Arg Gly Arg Ser Ala Ala Ser Arg Pro Thr 
1               5                   10                  15      


Gln Arg Pro Arg Ala Pro Ala Arg Ser Ala Ser Arg Pro Arg Arg Pro 
            20                  25                  30          


Val Gln 
        


<210>  45
<211>  63
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Cysteine deficient DKK2 OR Modified DKK2

<400>  45

Lys Gly Lys Asn Leu Gly Gln Ala Tyr Pro Ala Ser Ser Asp Lys Glu 
1               5                   10                  15      


Ser Glu Val Gly Arg Tyr Ser His Ser Pro His Gln Gly Ser Ser Ala 
            20                  25                  30          


Cys Met Val Ala Arg Arg Arg Arg Arg Arg Ala His Arg Asp Gly Met 
        35                  40                  45              


Ala Cys Pro Ser Thr Arg Ser Asn Asn Gly Ile Ala Ile Pro Val 
    50                  55                  60              


<210>  46
<211>  61
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Cysteine deficient DKK4 OR Modified DKK4

<400>  46

Asp Leu His Gly Ala Arg Lys Gly Ser Gln Ala Leu Ser Asp Thr Asp 
1               5                   10                  15      


Ser Asn Thr Arg Lys Phe Ser Leu Gln Pro Arg Asp Glu Lys Pro Phe 
            20                  25                  30          


Cys Ala Thr Ala Arg Arg Arg Arg Arg Arg Ala Gln Arg Asp Ala Met 
        35                  40                  45              


Ser Cys Pro Gly Thr Leu Ser Val Asn Asp Val Ala Thr 
    50                  55                  60      


<210>  47
<211>  279
<212>  PRT
<213>  Homo sapiens

<400>  47

Met Glu Ala Glu Glu Ala Ala Ala Lys Ala Ser Ser Glu Val Asn Leu 
1               5                   10                  15      


Ala Asn Leu Pro Pro Ser Tyr His Asn Glu Thr Asn Thr Asp Thr Lys 
            20                  25                  30          


Val Gly Asn Asn Thr Ile His Val His Arg Glu Ile His Lys Ile Thr 
        35                  40                  45              


Asn Asn Gln Thr Gly Gln Met Val Phe Ser Glu Thr Val Ile Thr Ser 
    50                  55                  60                  


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


Asp Cys Gly Pro Ser Met Tyr Cys Gln Phe Ala Ser Phe Gln Tyr Thr 
                85                  90                  95      


Cys Gln Pro Cys Arg Gly Gln Arg Met Leu Cys Thr Arg Asp Ser Glu 
            100                 105                 110         


Cys Cys Gly Asp Gln Leu Cys Val Trp Gly His Cys Thr Lys Met Ala 
        115                 120                 125             


Thr Arg Gly Ser Asn Gly Thr Ile Cys Asp Asn Gln Arg Asp Cys Gln 
    130                 135                 140                 


Pro Gly Leu Cys Cys Ala Phe Gln Arg Gly Leu Leu Phe Pro Val Cys 
145                 150                 155                 160 


Thr Pro Leu Pro Val Glu Gly Glu Leu Cys His Asp Pro Ala Ser Arg 
                165                 170                 175     


Leu Leu Asp Leu Ile Thr Trp Glu Leu Glu Pro Asp Gly Ala Leu Asp 
            180                 185                 190         


Arg Cys Pro Cys Ala Ser Gly Leu Leu Cys Gln Pro His Ser His Ser 
        195                 200                 205             


Leu Val Tyr Val Cys Lys Pro Thr Phe Val Gly Ser Arg Asp Gln Asp 
    210                 215                 220                 


Gly Glu Ile Leu Leu Pro Arg Glu Val Pro Asp Glu Tyr Glu Val Gly 
225                 230                 235                 240 


Ser Phe Met Glu Glu Val Arg Gln Glu Leu Glu Asp Leu Glu Arg Ser 
                245                 250                 255     


Leu Thr Glu Glu Met Ala Leu Arg Glu Pro Ala Ala Ala Ala Ala Ala 
            260                 265                 270         


Leu Leu Gly Gly Glu Glu Ile 
        275                 


<210>  48
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  N-terminal domain

<400>  48

Met Glu Ala Asp Glu Leu Leu Leu Lys Leu Asn Leu Ala Ala Thr Val 
1               5                   10                  15      


Gly Phe Ala Pro Pro 
            20      


<210>  49
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C-terminal domain

<400>  49

Thr Ser Gln Leu Leu Ile Ile Leu Gly Gly Asp Asp Ile 
1               5                   10              


<210>  50
<211>  137
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DKK3b peptide mimetic including SRP and poly-His tag

<400>  50

Met Thr Arg Leu Thr Val Leu Ala Leu Leu Ala Gly Leu Leu Ala Ser 
1               5                   10                  15      


Ser Arg Ala Gly Ser Gly Arg Gly His His His His His His Val Gly 
            20                  25                  30          


Thr Gly Ser Asn Ser Pro Gly Met Asp Ala Glu Asp Leu Leu Leu Lys 
        35                  40                  45              


Leu Asn Leu Ala Ala Thr Val Gly Thr Ala Pro Pro Lys Gly Lys Asn 
    50                  55                  60                  


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


Arg Tyr Ser His Ser Pro His Gln Gly Ser Ser Ala Cys Met Val Ala 
                85                  90                  95      


Arg Arg Arg Arg Arg Arg Ala His Arg Asp Gly Met Ala Cys Pro Ser 
            100                 105                 110         


Thr Arg Ser Asn Asn Gly Ile Ala Ile Pro Val Pro Thr Ala Ala Leu 
        115                 120                 125             


Leu Ile Ile Leu Gly Gly Asp Asp Ile 
    130                 135         


<210>  51
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Variant cell penetrating domain

<400>  51

Trp Leu Arg Arg Ile Lys Ala Trp Leu Arg Arg Ile Lys Ala 
1               5                   10                  


<210>  52
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Variant cell penetrating domain

<400>  52

Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg 
1               5                   10      


<210>  53
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Variant cell penetrating domain

<400>  53

Tyr Ala Arg Ala Ala Ala Arg Gln Ala Arg Ala 
1               5                   10      


<210>  54
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DKK1 cell penetrating domain

<400>  54

Cys Leu Ala Cys Arg Lys Arg Arg Lys Arg Cys Met Arg His Met Cys 
1               5                   10                  15      


Cys 
    


<210>  55
<211>  18
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DKK2 cell penetrating domain

<400>  55

Cys Met Val Cys Arg Arg Lys Lys Lys Arg Cys His Arg Asp Gly Met 
1               5                   10                  15      


Cys Cys 
        


<210>  56
<211>  18
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DKK3B cell penetrating domain

<400>  56

Cys Gln Pro Cys Arg Gly Gln Arg Met Leu Cys Thr Arg Asp Ser Glu 
1               5                   10                  15      


Cys Cys 
        


<210>  57
<211>  18
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DKK4 cell penetrating domain

<400>  57

Cys Ala Thr Cys Arg Gly Leu Arg Arg Arg Cys Gln Arg Asp Ala Met 
1               5                   10                  15      


Cys Cys 
        


<210>  58
<211>  326
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  cpDKK3b fusion protein

<400>  58

Met Arg Gly Ser Leu Lys His His His His His His Leu Lys Gly Met 
1               5                   10                  15      


Ala Ser Met Thr Gly Gly Gln Gln Met Lys Leu Gly Asp Ile Tyr Ala 
            20                  25                  30          


Arg Ala Ala Ala Arg Gln Ala Arg Ala Asp Ile Gly Gly Ser Thr Met 
        35                  40                  45              


Glu Ala Glu Glu Ala Ala Ala Lys Ala Ser Ser Glu Val Asn Leu Ala 
    50                  55                  60                  


Asn Leu Pro Pro Ser Tyr His Asn Glu Thr Asn Thr Asp Thr Lys Val 
65                  70                  75                  80  


Gly Asn Asn Thr Ile His Val His Arg Glu Ile His Lys Ile Thr Asn 
                85                  90                  95      


Asn Gln Thr Gly Gln Met Val Phe Ser Glu Thr Val Ile Thr Ser Val 
            100                 105                 110         


Gly Asp Glu Glu Gly Arg Arg Ser His Glu Cys Ile Ile Asp Glu Asp 
        115                 120                 125             


Cys Gly Pro Ser Met Tyr Cys Gln Phe Ala Ser Phe Gln Tyr Thr Cys 
    130                 135                 140                 


Gln Pro Cys Arg Gly Gln Arg Met Leu Cys Thr Arg Asp Ser Glu Cys 
145                 150                 155                 160 


Cys Gly Asp Gln Leu Cys Val Trp Gly His Cys Thr Lys Met Ala Thr 
                165                 170                 175     


Arg Gly Ser Asn Gly Thr Ile Cys Asp Asn Gln Arg Asp Cys Gln Pro 
            180                 185                 190         


Gly Leu Cys Cys Ala Phe Gln Arg Gly Leu Leu Phe Pro Val Cys Thr 
        195                 200                 205             


Pro Leu Pro Val Glu Gly Glu Leu Cys His Asp Pro Ala Ser Arg Leu 
    210                 215                 220                 


Leu Asp Leu Ile Thr Trp Glu Leu Glu Pro Asp Gly Ala Leu Asp Arg 
225                 230                 235                 240 


Cys Pro Cys Ala Ser Gly Leu Leu Cys Gln Pro His Ser His Ser Leu 
                245                 250                 255     


Val Tyr Val Cys Lys Pro Thr Phe Val Gly Ser Arg Asp Gln Asp Gly 
            260                 265                 270         


Glu Ile Leu Leu Pro Arg Glu Val Pro Asp Glu Tyr Glu Val Gly Ser 
        275                 280                 285             


Phe Met Glu Glu Val Arg Gln Glu Leu Glu Asp Leu Glu Arg Ser Leu 
    290                 295                 300                 


Thr Glu Glu Met Ala Leu Arg Glu Pro Ala Ala Ala Ala Ala Ala Leu 
305                 310                 315                 320 


Leu Gly Gly Glu Glu Ile 
                325     


<210>  59
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  N-terminal domain

<400>  59

Met Asp Ala Glu Asp Leu Leu Leu Lys Leu Asn Leu Ala Ala Thr Val 
1               5                   10                  15      


Gly Thr Ala Pro Pro 
            20      


<210>  60
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  N-terminal domain

<400>  60

Thr Ala Ala Leu Leu Ile Ile Leu Gly Gly Asp Asp Ile 
1               5                   10              


<210>  61
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  N-terminal domain

<400>  61

Asp Ala Glu Asp Leu Leu Leu Lys Leu Asn Leu Ala Ala Thr Val Gly 
1               5                   10                  15      


Thr Ala Pro Pro 
            20  


<210>  62
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  N-terminal domain


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  nonpolar amino acid other than proline; or is serine or 
       threonine; in certain aspects, is threonine, serine or a nonpolar
       amino acid other than proline and methionine; is alanine or 
       isoleucine

<400>  62

Xaa Asp Ala Glu Asp Leu Leu Leu Lys Leu Asn Leu Ala Ala Thr Val 
1               5                   10                  15      


Gly Thr Ala Pro Pro 
            20      


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

<220>
<223>  N-terminal domain

<400>  63

Ala Asp Ala Glu Asp Leu Leu Leu Lys Leu Asn Leu Ala Ala Thr Val 
1               5                   10                  15      


Gly Thr Ala Pro Pro 
            20      


<210>  64
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  N-terminal domain

<400>  64

Ile Asp Ala Glu Asp Leu Leu Leu Lys Leu Asn Leu Ala Ala Thr Val 
1               5                   10                  15      


Gly Thr Ala Pro Pro 
            20      


<210>  65
<211>  97
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DKK3b peptide mimetic

<400>  65

Asp Ala Glu Asp Leu Leu Leu Lys Leu Asn Leu Ala Ala Thr Val Gly 
1               5                   10                  15      


Thr Ala Pro Pro Lys Gly Lys Asn Leu Gly Gln Ala Tyr Pro Ala Ser 
            20                  25                  30          


Ser Asp Lys Glu Ser Glu Val Gly Arg Tyr Ser His Ser Pro His Gln 
        35                  40                  45              


Gly Ser Ser Ala Cys Met Val Ala Arg Arg Arg Arg Arg Arg Ala His 
    50                  55                  60                  


Arg Asp Gly Met Ala Cys Pro Ser Thr Arg Ser Asn Asn Gly Ile Ala 
65                  70                  75                  80  


Ile Pro Val Pro Thr Ala Ala Leu Leu Ile Ile Leu Gly Gly Asp Asp 
                85                  90                  95      


Ile 
    


<210>  66
<211>  98
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DKK3b peptide mimetic


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  nonpolar amino acid other than proline; or is serine or 
       threonine; in certain aspects, is threonine, serine or a nonpolar
       amino acid other than proline and methionine

<400>  66

Xaa Asp Ala Glu Asp Leu Leu Leu Lys Leu Asn Leu Ala Ala Thr Val 
1               5                   10                  15      


Gly Thr Ala Pro Pro Lys Gly Lys Asn Leu Gly Gln Ala Tyr Pro Ala 
            20                  25                  30          


Ser Ser Asp Lys Glu Ser Glu Val Gly Arg Tyr Ser His Ser Pro His 
        35                  40                  45              


Gln Gly Ser Ser Ala Cys Met Val Ala Arg Arg Arg Arg Arg Arg Ala 
    50                  55                  60                  


His Arg Asp Gly Met Ala Cys Pro Ser Thr Arg Ser Asn Asn Gly Ile 
65                  70                  75                  80  


Ala Ile Pro Val Pro Thr Ala Ala Leu Leu Ile Ile Leu Gly Gly Asp 
                85                  90                  95      


Asp Ile 
        


<210>  67
<211>  98
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DKK3b peptide mimetic

<400>  67

Ala Asp Ala Glu Asp Leu Leu Leu Lys Leu Asn Leu Ala Ala Thr Val 
1               5                   10                  15      


Gly Thr Ala Pro Pro Lys Gly Lys Asn Leu Gly Gln Ala Tyr Pro Ala 
            20                  25                  30          


Ser Ser Asp Lys Glu Ser Glu Val Gly Arg Tyr Ser His Ser Pro His 
        35                  40                  45              


Gln Gly Ser Ser Ala Cys Met Val Ala Arg Arg Arg Arg Arg Arg Ala 
    50                  55                  60                  


His Arg Asp Gly Met Ala Cys Pro Ser Thr Arg Ser Asn Asn Gly Ile 
65                  70                  75                  80  


Ala Ile Pro Val Pro Thr Ala Ala Leu Leu Ile Ile Leu Gly Gly Asp 
                85                  90                  95      


Asp Ile 
        


<210>  68
<211>  98
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DKK3b peptide mimetic

<400>  68

Ile Asp Ala Glu Asp Leu Leu Leu Lys Leu Asn Leu Ala Ala Thr Val 
1               5                   10                  15      


Gly Thr Ala Pro Pro Lys Gly Lys Asn Leu Gly Gln Ala Tyr Pro Ala 
            20                  25                  30          


Ser Ser Asp Lys Glu Ser Glu Val Gly Arg Tyr Ser His Ser Pro His 
        35                  40                  45              


Gln Gly Ser Ser Ala Cys Met Val Ala Arg Arg Arg Arg Arg Arg Ala 
    50                  55                  60                  


His Arg Asp Gly Met Ala Cys Pro Ser Thr Arg Ser Asn Asn Gly Ile 
65                  70                  75                  80  


Ala Ile Pro Val Pro Thr Ala Ala Leu Leu Ile Ile Leu Gly Gly Asp 
                85                  90                  95      


Asp Ile 
        


<210>  69
<211>  53
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DKK2 variant

<400>  69

Ala Ser Ser Asp Lys Glu Ser Glu Val Gly Arg Tyr Ser His Ser Pro 
1               5                   10                  15      


His Gln Gly Ser Ser Ala Cys Met Val Ala Arg Arg Arg Arg Arg Arg 
            20                  25                  30          


Ala His Arg Asp Gly Met Ala Cys Pro Ser Thr Arg Ser Asn Asn Gly 
        35                  40                  45              


Ile Ala Ile Pro Val 
    50              


<210>  70
<211>  98
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DKK3b peptide mimetic


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  nonpolar amino acid other than proline; or is serine or 
       threonine; in certain aspects, is threonine, serine or a nonpolar
       amino acid other than proline and methionine

<220>
<221>  MISC_FEATURE
<222>  (54)..(54)
<223>  serine or alanine

<220>
<221>  MISC_FEATURE
<222>  (71)..(71)
<223>  serine or alanine

<400>  70

Xaa Asp Ala Glu Asp Leu Leu Leu Lys Leu Asn Leu Ala Ala Thr Val 
1               5                   10                  15      


Gly Thr Ala Pro Pro Lys Gly Lys Asn Leu Gly Gln Ala Tyr Pro Ala 
            20                  25                  30          


Ser Ser Asp Lys Glu Ser Glu Val Gly Arg Tyr Ser His Ser Pro His 
        35                  40                  45              


Gln Gly Ser Ser Ala Xaa Met Val Ala Arg Arg Arg Arg Arg Arg Ala 
    50                  55                  60                  


His Arg Asp Gly Met Ala Xaa Pro Ser Thr Arg Ser Asn Asn Gly Ile 
65                  70                  75                  80  


Ala Ile Pro Val Pro Thr Ala Ala Leu Leu Ile Ile Leu Gly Gly Asp 
                85                  90                  95      


Asp Ile 
        


<210>  71
<211>  98
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DKK3b peptide mimetic


<220>
<221>  MISC_FEATURE
<222>  (54)..(54)
<223>  serine or alanine

<220>
<221>  MISC_FEATURE
<222>  (71)..(71)
<223>  serine or alanine

<400>  71

Ala Asp Ala Glu Asp Leu Leu Leu Lys Leu Asn Leu Ala Ala Thr Val 
1               5                   10                  15      


Gly Thr Ala Pro Pro Lys Gly Lys Asn Leu Gly Gln Ala Tyr Pro Ala 
            20                  25                  30          


Ser Ser Asp Lys Glu Ser Glu Val Gly Arg Tyr Ser His Ser Pro His 
        35                  40                  45              


Gln Gly Ser Ser Ala Xaa Met Val Ala Arg Arg Arg Arg Arg Arg Ala 
    50                  55                  60                  


His Arg Asp Gly Met Ala Xaa Pro Ser Thr Arg Ser Asn Asn Gly Ile 
65                  70                  75                  80  


Ala Ile Pro Val Pro Thr Ala Ala Leu Leu Ile Ile Leu Gly Gly Asp 
                85                  90                  95      


Asp Ile 
        


<210>  72
<211>  98
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DKK3b peptide mimetic


<220>
<221>  MISC_FEATURE
<222>  (54)..(54)
<223>  serine or alanine

<220>
<221>  MISC_FEATURE
<222>  (71)..(71)
<223>  serine or alanine

<400>  72

Ile Asp Ala Glu Asp Leu Leu Leu Lys Leu Asn Leu Ala Ala Thr Val 
1               5                   10                  15      


Gly Thr Ala Pro Pro Lys Gly Lys Asn Leu Gly Gln Ala Tyr Pro Ala 
            20                  25                  30          


Ser Ser Asp Lys Glu Ser Glu Val Gly Arg Tyr Ser His Ser Pro His 
        35                  40                  45              


Gln Gly Ser Ser Ala Xaa Met Val Ala Arg Arg Arg Arg Arg Arg Ala 
    50                  55                  60                  


His Arg Asp Gly Met Ala Xaa Pro Ser Thr Arg Ser Asn Asn Gly Ile 
65                  70                  75                  80  


Ala Ile Pro Val Pro Thr Ala Ala Leu Leu Ile Ile Leu Gly Gly Asp 
                85                  90                  95      


Asp Ile 
        


<210>  73
<211>  53
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DKK2 variant

<400>  73

Cys Ser Ser Asp Lys Glu Cys Glu Val Gly Arg Tyr Cys His Ser Pro 
1               5                   10                  15      


His Gln Gly Ser Ser Ala Cys Met Val Cys Arg Arg Arg Arg Arg Arg 
            20                  25                  30          


Cys His Arg Asp Gly Met Cys Cys Pro Ser Thr Arg Cys Asn Asn Gly 
        35                  40                  45              


Ile Cys Ile Pro Val 
    50              


<210>  74
<211>  53
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  N-1 domain variant


<220>
<221>  MISC_FEATURE
<222>  (23)..(23)
<223>  alanine or serine

<220>
<221>  MISC_FEATURE
<222>  (40)..(40)
<223>  alanine or serine

<400>  74

Ala Ser Ser Asp Lys Glu Ser Glu Val Gly Arg Tyr Ser His Ser Pro 
1               5                   10                  15      


His Gln Gly Ser Ser Ala Xaa Met Val Ala Arg Arg Arg Arg Arg Arg 
            20                  25                  30          


Ala His Arg Asp Gly Met Ala Xaa Pro Ser Thr Arg Ser Asn Asn Gly 
        35                  40                  45              


Ile Ala Ile Pro Val 
    50              


<210>  75
<211>  98
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DKK3b peptide mimetic

<400>  75

Ile Asp Ala Glu Asp Leu Leu Leu Lys Leu Asn Leu Ala Ala Thr Val 
1               5                   10                  15      


Gly Thr Ala Pro Pro Lys Gly Lys Asn Leu Gly Gln Ala Tyr Pro Ala 
            20                  25                  30          


Ser Ser Asp Lys Glu Ser Glu Val Gly Arg Tyr Ser His Ser Pro His 
        35                  40                  45              


Gln Gly Ser Ser Ala Ser Met Val Ala Arg Arg Arg Arg Arg Arg Ala 
    50                  55                  60                  


His Arg Asp Gly Met Ala Ala Pro Ser Thr Arg Ser Asn Asn Gly Ile 
65                  70                  75                  80  


Ala Ile Pro Val Pro Thr Ala Ala Leu Leu Ile Ile Leu Gly Gly Asp 
                85                  90                  95      


Asp Ile 
        


<210>  76
<211>  98
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DKK3b peptide mimetic

<400>  76

Ile Asp Ala Glu Asp Leu Leu Leu Lys Leu Asn Leu Ala Ala Thr Val 
1               5                   10                  15      


Gly Thr Ala Pro Pro Lys Gly Lys Asn Leu Gly Gln Ala Tyr Pro Ala 
            20                  25                  30          


Ser Ser Asp Lys Glu Ser Glu Val Gly Arg Tyr Ser His Ser Pro His 
        35                  40                  45              


Gln Gly Ser Ser Ala Ala Met Val Ala Arg Arg Arg Arg Arg Arg Ala 
    50                  55                  60                  


His Arg Asp Gly Met Ala Ser Pro Ser Thr Arg Ser Asn Asn Gly Ile 
65                  70                  75                  80  


Ala Ile Pro Val Pro Thr Ala Ala Leu Leu Ile Ile Leu Gly Gly Asp 
                85                  90                  95      


Asp Ile 
        


<210>  77
<211>  98
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DKK3b peptide mimetic

<400>  77

Ala Asp Ala Glu Asp Leu Leu Leu Lys Leu Asn Leu Ala Ala Thr Val 
1               5                   10                  15      


Gly Thr Ala Pro Pro Lys Gly Lys Asn Leu Gly Gln Ala Tyr Pro Ala 
            20                  25                  30          


Ser Ser Asp Lys Glu Ser Glu Val Gly Arg Tyr Ser His Ser Pro His 
        35                  40                  45              


Gln Gly Ser Ser Ala Ser Met Val Ala Arg Arg Arg Arg Arg Arg Ala 
    50                  55                  60                  


His Arg Asp Gly Met Ala Ala Pro Ser Thr Arg Ser Asn Asn Gly Ile 
65                  70                  75                  80  


Ala Ile Pro Val Pro Thr Ala Ala Leu Leu Ile Ile Leu Gly Gly Asp 
                85                  90                  95      


Asp Ile 
        


<210>  78
<211>  98
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DKK3b peptide mimetic

<400>  78

Ala Asp Ala Glu Asp Leu Leu Leu Lys Leu Asn Leu Ala Ala Thr Val 
1               5                   10                  15      


Gly Thr Ala Pro Pro Lys Gly Lys Asn Leu Gly Gln Ala Tyr Pro Ala 
            20                  25                  30          


Ser Ser Asp Lys Glu Ser Glu Val Gly Arg Tyr Ser His Ser Pro His 
        35                  40                  45              


Gln Gly Ser Ser Ala Ala Met Val Ala Arg Arg Arg Arg Arg Arg Ala 
    50                  55                  60                  


His Arg Asp Gly Met Ala Ser Pro Ser Thr Arg Ser Asn Asn Gly Ile 
65                  70                  75                  80  


Ala Ile Pro Val Pro Thr Ala Ala Leu Leu Ile Ile Leu Gly Gly Asp 
                85                  90                  95      


Asp Ile 
        


<210>  79
<211>  98
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DKK3b peptide mimetic

<400>  79

Met Asp Ala Glu Asp Leu Leu Leu Lys Leu Asn Leu Ala Ala Thr Val 
1               5                   10                  15      


Gly Thr Ala Pro Pro Lys Gly Lys Asn Leu Gly Gln Ala Tyr Pro Ala 
            20                  25                  30          


Ser Ser Asp Lys Glu Ser Glu Val Gly Arg Tyr Ser His Ser Pro His 
        35                  40                  45              


Gln Gly Ser Ser Ala Ser Met Val Ala Arg Arg Arg Arg Arg Arg Ala 
    50                  55                  60                  


His Arg Asp Gly Met Ala Ala Pro Ser Thr Arg Ser Asn Asn Gly Ile 
65                  70                  75                  80  


Ala Ile Pro Val Pro Thr Ala Ala Leu Leu Ile Ile Leu Gly Gly Asp 
                85                  90                  95      


Asp Ile 
        


<210>  80
<211>  98
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DKK3b peptide mimetic

<400>  80

Met Asp Ala Glu Asp Leu Leu Leu Lys Leu Asn Leu Ala Ala Thr Val 
1               5                   10                  15      


Gly Thr Ala Pro Pro Lys Gly Lys Asn Leu Gly Gln Ala Tyr Pro Ala 
            20                  25                  30          


Ser Ser Asp Lys Glu Ser Glu Val Gly Arg Tyr Ser His Ser Pro His 
        35                  40                  45              


Gln Gly Ser Ser Ala Ala Met Val Ala Arg Arg Arg Arg Arg Arg Ala 
    50                  55                  60                  


His Arg Asp Gly Met Ala Ser Pro Ser Thr Arg Ser Asn Asn Gly Ile 
65                  70                  75                  80  


Ala Ile Pro Val Pro Thr Ala Ala Leu Leu Ile Ile Leu Gly Gly Asp 
                85                  90                  95      


Asp Ile 
        


<210>  81
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Poly-Arg CPP


<220>
<221>  MISC_FEATURE
<222>  (7)..(12)
<223>  Xaa at positions 7-12 are Arg and up to five of them may be 
       absent

<400>  81

Arg Arg Arg Arg Arg Arg Xaa Xaa Xaa Xaa Xaa Xaa 
1               5                   10          


