                         SEQUENCE LISTING

<110>  VIB vzw
       D.Collen Research Foundation vzw
 
<120>  Inhibitors of Prolyl-hydroxylase 1 for the treatment of skeletal 
       muscle degeneration

<130>  PCA/PHD/V227

<150>  EP06100440.4
<151>  2006-01-17

<160>  27    

<170>  PatentIn version 3.3

<210>  1
<211>  2111
<212>  DNA
<213>  Homo sapiens

<400>  1
gctttcccct gcctgcctgt ctctagtttc tctcacatcc cttttttttt ttcctttctc     60

tagccaccct gaagggtccc ttcccaagcc cttagggacc gcagaggact tggggaccag    120

caagcaaccc ccagggcacg agaagagctc ttgctgtctg ccctgcctca ccctgcccca    180

cgccaggccc ggtggccccc agctgcatca agtggaggcg gaggaggagg cggaggaggg    240

tggcaccatg ggcccgggcg gtgccctcca tgcccggggg atgaagacac tgctgccatg    300

gacagcccgt gccagccgca gcccctaagt caggctctcc ctcagttacc agggtcttcg    360

tcagagccct tggagcctga gcctggccgg gccaggatgg gagtggagag ttacctgccc    420

tgtcccctgc tcccctccta ccactgtcca ggagtgccta gtgaggcctc ggcagggagt    480

gggaccccca gagccacagc cacctctacc actgccagcc ctcttcggga cggttttggc    540

gggcaggatg gtggtgagct gcggccgctg cagagtgaag gcgctgcagc gctggtcacc    600

aaggggtgcc agcgattggc agcccagggc gcacggcctg aggcccccaa acggaaatgg    660

gccgaggatg gtggggatgc cccttcaccc agcaaacggc cctgggccag gcaagagaac    720

caggaggcag agcgggaggg tggcatgagc tgcagctgca gcagtggcag tggtgaggcc    780

agtgctgggc tgatggagga ggcgctgccc tctgcgcccg agcgcctggc cctggactat    840

atcgtgccct gcatgcggta ctacggcatc tgcgtcaagg acagcttcct gggggcagca    900

ctgggcggtc gcgtgctggc cgaggtggag gccctcaaac ggggtgggcg cctgcgagac    960

gggcagctag tgagccagag ggcgatcccg ccgcgcagca tccgtgggga ccagattgcc   1020

tgggtggaag gccatgaacc aggctgtcga agcattggtg ccctcatggc ccatgtggac   1080

gccgtcatcc gccactgcgc agggcggctg ggcagctatg tcatcaacgg gcgcaccaag   1140

gccatggtgg cgtgttaccc aggcaacggg ctcgggtacg taaggcacgt tgacaatccc   1200

cacggcgatg ggcgctgcat cacctgtatc tattacctga atcagaactg ggacgttaag   1260

gtgcatggcg gcctgctgca gatcttccct gagggccggc ccgtggtagc caacatcgag   1320

ccactctttg accggttgct cattttctgg tctgaccggc ggaaccccca cgaggtgaag   1380

ccagcctatg ccaccaggta cgccatcact gtctggtatt ttgatgccaa ggagcgggca   1440

gcagccaaag acaagtatca gctagcatca ggacagaaag gtgtccaagt acctgtatca   1500

cagccgccta cgcccaccta gtggccagtc ccagagccgc atggcagaca gcttaaatga   1560

cttcaggaga gccctgggcc tgtgctggct gctccttccc tgccaccgct gctgcttctg   1620

actttgcctc tgtcctgcct ggtgtggagg gctctgtctg ttgctgagga ccaaggagga   1680

gaagagacct ttgctgcccc atcatggggg ctggggttgt cacctggaca gggggcagcc   1740

gtggaggcca ccgttaccaa ctgaagctgg gggcctgggt cctaccctgt ctggtcatga   1800

ccccattagg tatggagagc tgggaggagg cattgtcact tcccaccagg atgcaggact   1860

tggggttgag gtgagtcatg gcctcttgct ggcaatgggg tgggaggagt acccccaagt   1920

cctctcactc ctccagcctg gaatgtgaag tgactcccca acccctttgg ccatggcagg   1980

caccttttgg actgggctgc cactgcttgg gcagagtaaa aggtgccagg aggagcatgg   2040

gtgtggaagt cctgtcagcc aagaaataaa agtttacctc agagctgcaa aaaaaaaaaa   2100

aaaaaaaaaa a                                                        2111


<210>  2
<211>  407
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Asp Ser Pro Cys Gln Pro Gln Pro Leu Ser Gln Ala Leu Pro Gln 
1               5                   10                  15      


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


Arg Met Gly Val Glu Ser Tyr Leu Pro Cys Pro Leu Leu Pro Ser Tyr 
        35                  40                  45              


His Cys Pro Gly Val Pro Ser Glu Ala Ser Ala Gly Ser Gly Thr Pro 
    50                  55                  60                  


Arg Ala Thr Ala Thr Ser Thr Thr Ala Ser Pro Leu Arg Asp Gly Phe 
65                  70                  75                  80  


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


Ala Ala Leu Val Thr Lys Gly Cys Gln Arg Leu Ala Ala Gln Gly Ala 
            100                 105                 110         


Arg Pro Glu Ala Pro Lys Arg Lys Trp Ala Glu Asp Gly Gly Asp Ala 
        115                 120                 125             


Pro Ser Pro Ser Lys Arg Pro Trp Ala Arg Gln Glu Asn Gln Glu Ala 
    130                 135                 140                 


Glu Arg Glu Gly Gly Met Ser Cys Ser Cys Ser Ser Gly Ser Gly Glu 
145                 150                 155                 160 


Ala Ser Ala Gly Leu Met Glu Glu Ala Leu Pro Ser Ala Pro Glu Arg 
                165                 170                 175     


Leu Ala Leu Asp Tyr Ile Val Pro Cys Met Arg Tyr Tyr Gly Ile Cys 
            180                 185                 190         


Val Lys Asp Ser Phe Leu Gly Ala Ala Leu Gly Gly Arg Val Leu Ala 
        195                 200                 205             


Glu Val Glu Ala Leu Lys Arg Gly Gly Arg Leu Arg Asp Gly Gln Leu 
    210                 215                 220                 


Val Ser Gln Arg Ala Ile Pro Pro Arg Ser Ile Arg Gly Asp Gln Ile 
225                 230                 235                 240 


Ala Trp Val Glu Gly His Glu Pro Gly Cys Arg Ser Ile Gly Ala Leu 
                245                 250                 255     


Met Ala His Val Asp Ala Val Ile Arg His Cys Ala Gly Arg Leu Gly 
            260                 265                 270         


Ser Tyr Val Ile Asn Gly Arg Thr Lys Ala Met Val Ala Cys Tyr Pro 
        275                 280                 285             


Gly Asn Gly Leu Gly Tyr Val Arg His Val Asp Asn Pro His Gly Asp 
    290                 295                 300                 


Gly Arg Cys Ile Thr Cys Ile Tyr Tyr Leu Asn Gln Asn Trp Asp Val 
305                 310                 315                 320 


Lys Val His Gly Gly Leu Leu Gln Ile Phe Pro Glu Gly Arg Pro Val 
                325                 330                 335     


Val Ala Asn Ile Glu Pro Leu Phe Asp Arg Leu Leu Ile Phe Trp Ser 
            340                 345                 350         


Asp Arg Arg Asn Pro His Glu Val Lys Pro Ala Tyr Ala Thr Arg Tyr 
        355                 360                 365             


Ala Ile Thr Val Trp Tyr Phe Asp Ala Lys Glu Arg Ala Ala Ala Lys 
    370                 375                 380                 


Asp Lys Tyr Gln Leu Ala Ser Gly Gln Lys Gly Val Gln Val Pro Val 
385                 390                 395                 400 


Ser Gln Pro Pro Thr Pro Thr 
                405         


<210>  3
<211>  2034
<212>  DNA
<213>  Mus musculus

<400>  3
ccacgcgtcc gggcggcgcc gaggccggag gaaaaagctc gccaccccca tcagtccctt     60

ctcaagctcc tagagacaac tgtggacttg gggaccagcg agcaccccca gagcactaga    120

ggagcccctg ctgcctgccc tgcctcaccc tgccccacac gaggcccagc ggccccgggc    180

tgcatcaagt ggaggaggag gaggcggagg agggtggcac catgggcccg ggccgtgccc    240

tccatgcccg ggggatgaag acactgctgc catggacagc ccgtgccagc cgcaggccct    300

gaatcaagct ctccctcagt tgccagggtc tgtgtcagag tccttggagt ctagccgagc    360

cagaatgggg gtggagagtt acctgccctg ccctctgctc ccggcctatc accgtccagg    420

agcatctggg gaggcctcgg ctggcaatgg gacccccaga accacagcca ctgctactac    480

gaccactgcc agtcccctgc gggagggctt tggtgggcag gatggtggtg agctttggcc    540

actgcagagt gaaggtgctg ctgcgttggt caccaaggag tgccagcgac tggcggccca    600

gggtgcccgg cctgaggccc ccaaacggaa gtgggccaag gatggtgggg atgccccttc    660

acccagcaag cgaccgtggg ccaggcaaga gaaccaggag gccaaggggg aaagtggtat    720

gggctgtgac agcggtgcca gcaacagcag cagcagcagc agcaacacta ccagtagcag    780

tggcgaggca agtgctaggc tgagggagga agtccagccc tctgcacctg agcgcctggc    840

cctggactat attgtgcctt gcatgcggta ctatggtatc tgtgtcaagg acaacttctt    900

gggggcagta ctgggtggcc gtgtgctggc tgaggtggaa gccctgaagt ggggcgggcg    960

tcttcgtgat gggcaactag tgagccagcg ggcgatccca ccgcgcagca ttcgtgggga   1020

ccagattgcc tgggtagaag gtcacgagcc aggctgccgg agcattggtg ccctcatggc   1080

tcacgtggac gcagtaatcc gccactgtgc agggcggctg ggcaactacg tcatcaatgg   1140

gcgcaccaag gccatggtgg cgtgttatcc aggcaatggg ctcgggtacg tgaggcatgt   1200

tgacaatccc cacggcgatg ggcgctgcat cacctgtatc tattacctga atcagaactg   1260

ggatgttaag gtgcatggcg gcctgctgca gatcttcccc gagggtcggc cagtggtagc   1320

caacatcgag ccactctttg accggttgct cattttctgg tctgaccgac ggaacccaca   1380

tgaggtgaag ccagcctatg ccaccaggta cgccatcact gtctggtatt ttgatgccaa   1440

ggaacgggca gcagccagag acaagtatca gctagcatcg ggacagaaag gtgttcaagt   1500

accagtatca cagccaacta cacctaccta atggccagcc ccagagctgc gtggaccagc   1560

agcagctcct gcctcagtgc ccgctccttt cctgccactg ctgctgcttc tggcttgcct   1620

ctgtactgtg tggtgtggag ggcactaagt atcactgagg agcaacaagg agagacctct   1680

gctgccccgt gagcgagcgg tgctgggttt tgacctgggc agtggccagt gtggctggcg   1740

gtcatgactg gtggctgtgt ctggtccgtt gagtgtagag ctgagaagag gcaggatttg   1800

gggttgaggt gagtcatggc ctcttgctgg aaaggtgtgt tggggtgtgg gtgtcatctc   1860

accctcgtcc ccactcctcc ggcctggaat gtgaagtgac tccccagccc ctttggctgt   1920

ggcagtgtat ggactgggct gccactgtct gggcagagta gggtgccatg acgagcatgg   1980

gtatggaggt tctgccagcc aagaaataaa agtttacctc agagctgcaa aaaa         2034


<210>  4
<211>  419
<212>  PRT
<213>  Mus musculus

<400>  4

Met Asp Ser Pro Cys Gln Pro Gln Ala Leu Asn Gln Ala Leu Pro Gln 
1               5                   10                  15      


Leu Pro Gly Ser Val Ser Glu Ser Leu Glu Ser Ser Arg Ala Arg Met 
            20                  25                  30          


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


Pro Gly Ala Ser Gly Glu Ala Ser Ala Gly Asn Gly Thr Pro Arg Thr 
    50                  55                  60                  


Thr Ala Thr Ala Thr Thr Thr Thr Ala Ser Pro Leu Arg Glu Gly Phe 
65                  70                  75                  80  


Gly Gly Gln Asp Gly Gly Glu Leu Trp Pro Leu Gln Ser Glu Gly Ala 
                85                  90                  95      


Ala Ala Leu Val Thr Lys Glu Cys Gln Arg Leu Ala Ala Gln Gly Ala 
            100                 105                 110         


Arg Pro Glu Ala Pro Lys Arg Lys Trp Ala Lys Asp Gly Gly Asp Ala 
        115                 120                 125             


Pro Ser Pro Ser Lys Arg Pro Trp Ala Arg Gln Glu Asn Gln Glu Ala 
    130                 135                 140                 


Lys Gly Glu Ser Gly Met Gly Cys Asp Ser Gly Ala Ser Asn Ser Ser 
145                 150                 155                 160 


Ser Ser Ser Ser Asn Thr Thr Ser Ser Ser Gly Glu Ala Ser Ala Arg 
                165                 170                 175     


Leu Arg Glu Glu Val Gln Pro Ser Ala Pro Glu Arg Leu Ala Leu Asp 
            180                 185                 190         


Tyr Ile Val Pro Cys Met Arg Tyr Tyr Gly Ile Cys Val Lys Asp Asn 
        195                 200                 205             


Phe Leu Gly Ala Val Leu Gly Gly Arg Val Leu Ala Glu Val Glu Ala 
    210                 215                 220                 


Leu Lys Trp Gly Gly Arg Leu Arg Asp Gly Gln Leu Val Ser Gln Arg 
225                 230                 235                 240 


Ala Ile Pro Pro Arg Ser Ile Arg Gly Asp Gln Ile Ala Trp Val Glu 
                245                 250                 255     


Gly His Glu Pro Gly Cys Arg Ser Ile Gly Ala Leu Met Ala His Val 
            260                 265                 270         


Asp Ala Val Ile Arg His Cys Ala Gly Arg Leu Gly Asn Tyr Val Ile 
        275                 280                 285             


Asn Gly Arg Thr Lys Ala Met Val Ala Cys Tyr Pro Gly Asn Gly Leu 
    290                 295                 300                 


Gly Tyr Val Arg His Val Asp Asn Pro His Gly Asp Gly Arg Cys Ile 
305                 310                 315                 320 


Thr Cys Ile Tyr Tyr Leu Asn Gln Asn Trp Asp Val Lys Val His Gly 
                325                 330                 335     


Gly Leu Leu Gln Ile Phe Pro Glu Gly Arg Pro Val Val Ala Asn Ile 
            340                 345                 350         


Glu Pro Leu Phe Asp Arg Leu Leu Ile Phe Trp Ser Asp Arg Arg Asn 
        355                 360                 365             


Pro His Glu Val Lys Pro Ala Tyr Ala Thr Arg Tyr Ala Ile Thr Val 
    370                 375                 380                 


Trp Tyr Phe Asp Ala Lys Glu Arg Ala Ala Ala Arg Asp Lys Tyr Gln 
385                 390                 395                 400 


Leu Ala Ser Gly Gln Lys Gly Val Gln Val Pro Val Ser Gln Pro Thr 
                405                 410                 415     


Thr Pro Thr 
            


<210>  5
<211>  55
<212>  DNA
<213>  Artificial

<220>
<223>  Short hairpin sequence against PHD1

<400>  5
caccgctgca tcacctgtat ctatttctct tgaaaataga tacaggtgat gcagc          55


<210>  6
<211>  55
<212>  DNA
<213>  Artificial

<220>
<223>  Short hairpin sequence to knockdown PHD1 expression

<400>  6
caccgctgca tcacctgtat ctatttctct tgaaaataga tacaggtgat gcagc          55


<210>  7
<211>  55
<212>  DNA
<213>  Artificial

<220>
<223>  Short hairpin sequence control

<400>  7
caccgcttaa cccgtattgc ctatttctct tgaaaatagg caatacgggt taagc          55


<210>  8
<211>  55
<212>  DNA
<213>  Homo sapiens

<400>  8
caccgctgca tcacctgtat ctatttctct tgaaaataga tacaggtgat gcagc          55


<210>  9
<211>  55
<212>  DNA
<213>  Homo sapiens

<400>  9
caccgccaac atcgagccac tcttttctct tgaaaaagag tggctcgatg ttggc          55


<210>  10
<211>  23
<212>  DNA
<213>  Artificial

<220>
<223>  Forward primer PHD1

<400>  10
ggtacgtgag gcatgttgac aat                                             23


<210>  11
<211>  27
<212>  DNA
<213>  Artificial

<220>
<223>  Reverse primer PHD1

<400>  11
cttaacatcc cagttctgat tcaggta                                         27


<210>  12
<211>  18
<212>  DNA
<213>  Artificial

<220>
<223>  probe PHD1

<400>  12
cccacggcga tgggcgct                                                   18


<210>  13
<211>  24
<212>  DNA
<213>  Artificial

<220>
<223>  Forward primer PHD2

<400>  13
agtcccatga agtgatcaag ttca                                            24


<210>  14
<211>  19
<212>  DNA
<213>  Artificial

<220>
<223>  Reverse primer PHD2

<400>  14
atccgcatga tctgcatgg                                                  19


<210>  15
<211>  25
<212>  DNA
<213>  Artificial

<220>
<223>  Probe PHD2

<400>  15
tgcccacgtc agagagcaac atcac                                           25


<210>  16
<211>  30
<212>  DNA
<213>  Artificial

<220>
<223>  Forward primer PHD3

<400>  16
ttatcagact gaagagctac tgtaatgatc                                      30


<210>  17
<211>  30
<212>  DNA
<213>  Artificial

<220>
<223>  Reverse primer PHD3

<400>  17
ttaccagtgt caattatatc ttcaacaatc                                      30


<210>  18
<211>  34
<212>  DNA
<213>  Artificial

<220>
<223>  Probe PHD3

<400>  18
tgagagatca tctccaccaa taactttatg tccc                                 34


<210>  19
<211>  21
<212>  DNA
<213>  Artificial

<220>
<223>  Forward primer Glut1

<400>  19
gggcatgtgc ttccagtatg t                                               21


<210>  20
<211>  20
<212>  DNA
<213>  Artificial

<220>
<223>  Reverse primer Glut1

<400>  20
acgaggagca ccgtgaagat                                                 20


<210>  21
<211>  24
<212>  DNA
<213>  Artificial

<220>
<223>  Probe Glut1

<400>  21
caactgtgcg gcccctacgt cttc                                            24


<210>  22
<211>  19
<212>  DNA
<213>  Artificial

<220>
<223>  Forward primer Glut4

<400>  22
gatctgccgc tccgaaaag                                                  19


<210>  23
<211>  20
<212>  DNA
<213>  Artificial

<220>
<223>  Reverse primer Glut4

<400>  23
ggaagtctct cccacggtga                                                 20


<210>  24
<211>  25
<212>  DNA
<213>  Artificial

<220>
<223>  Probe Glut4

<400>  24
taccaagcct cccagccctt acgct                                           25


<210>  25
<211>  20
<212>  DNA
<213>  Artificial

<220>
<223>  Forward primer alfa-actin

<400>  25
agagggaaat cgtgcgtgac                                                 20


<210>  26
<211>  21
<212>  DNA
<213>  Artificial

<220>
<223>  Reverse primer alfa-actin

<400>  26
caatagtgat gacctggccg t                                               21


<210>  27
<211>  23
<212>  DNA
<213>  Artificial

<220>
<223>  Probe alfa-actin

<400>  27
cactgccgca tcctcttcct ccc                                             23


