SEQUENCE LISTING 


<110> SYMRISE AG, BASF SE


<120> Niedermolekulare Modulatoren des Klte-Menthol-Rezeptors TRPM8 


<130> M/50228 


<160> 2 


<170> PatentIn version 3.3 


<210> 1 


<211> 5621 


<212> DNA 


<213> Homo sapiens 


<400> 1 
aagaaaatcc tgcttgacaa aaaccgtcac ttaggaaaag atgtcctttc gggcagccag 60 
gctcagcatg aggaacagaa ggaatgacac tctggacagc acccggaccc tgtactccag 120 
cgcgtctcgg agcacagact tgtcttacag tgaaagcgac ttggtgaatt ttattcaagc 180 
aaattttaag aaacgagaat gtgtcttctt taccaaagat tccaaggcca cggagaatgt 240 
gtgcaagtgt ggctatgccc agagccagca catggaaggc acccagatca accaaagtga 300 
gaaatggaac tacaagaaac acaccaagga atttcctacc gacgcctttg gggatattca 360 
gtttgagaca ctggggaaga aagggaagta tatacgtctg tcctgcgaca cggacgcgga 420 
aatcctttac gagctgctga cccagcactg gcacctgaaa acacccaacc tggtcatttc 480 
tgtgaccggg ggcgccaaga acttcgccct gaagccgcgc atgcgcaaga tcttcagccg 540 
gctcatctac atcgcgcagt ccaaaggtgc ttggattctc acgggaggca cccattatgg 600 
cctgatgaag tacatcgggg aggtggtgag agataacacc atcagcagga gttcagagga 660 
gaatattgtg gccattggca tagcagcttg gggcatggtc tccaaccggg acaccctcat 720 
caggaattgc gatgctgagg gctatttttt agcccagtac cttatggatg acttcacaag 780 
agatccactg tatatcctgg acaacaacca cacacatttg ctgctcgtgg acaatggctg 840 
tcatggacat cccactgtcg aagcaaagct ccggaatcag ctagagaagt atatctctga 900 
gcgcactatt caagattcca actatggtgg caagatcccc attgtgtgtt ttgcccaagg 960 
aggtggaaaa gagactttga aagccatcaa tacctccatc aaaaataaaa ttccttgtgt 1020 
ggtggtggaa ggctcgggcc agatcgctga tgtgatcgct agcctggtgg aggtggagga 1080 
tgccctgaca tcttctgccg tcaaggagaa gctggtgcgc tttttacccc gcacggtgtc 1140 
ccggctgcct gaggaggaga ctgagagttg gatcaaatgg ctcaaagaaa ttctcgaatg 1200 
ttctcaccta ttaacagtta ttaaaatgga agaagctggg gatgaaattg tgagcaatgc 1260 
catctcctac gctctataca aagccttcag caccagtgag caagacaagg ataactggaa 1320 
tgggcagctg aagcttctgc tggagtggaa ccagctggac ttagccaatg atgagatttt 1380 
caccaatgac cgccgatggg agtctgctga ccttcaagaa gtcatgttta cggctctcat 1440 
aaaggacaga cccaagtttg tccgcctctt tctggagaat ggcttgaacc tacggaagtt 1500 
tctcacccat gatgtcctca ctgaactctt ctccaaccac ttcagcacgc ttgtgtaccg 1560 
gaatctgcag atcgccaaga attcctataa tgatgccctc ctcacgtttg tctggaaact 1620 
ggttgcgaac ttccgaagag gcttccggaa ggaagacaga aatggccggg acgagatgga 1680 
catagaactc cacgacgtgt ctcctattac tcggcacccc ctgcaagctc tcttcatctg 1740 
ggccattctt cagaataaga aggaactctc caaagtcatt tgggagcaga ccaggggctg 1800 
cactctggca gccctgggag ccagcaagct tctgaagact ctggccaaag tgaagaacga 1860 
catcaatgct gctggggagt ccgaggagct ggctaatgag tacgagaccc gggctgttga 1920 
gctgttcact gagtgttaca gcagcgatga agacttggca gaacagctgc tggtctattc 1980 
ctgtgaagct tggggtggaa gcaactgtct ggagctggcg gtggaggcca cagaccagca 2040 
tttcatcgcc cagcctgggg tccagaattt tctttctaag caatggtatg gagagatttc 2100 
ccgagacacc aagaactgga agattatcct gtgtctgttt attataccct tggtgggctg 2160 
tggctttgta tcatttagga agaaacctgt cgacaagcac aagaagctgc tttggtacta 2220 
tgtggcgttc ttcacctccc ccttcgtggt cttctcctgg aatgtggtct tctacatcgc 2280 
cttcctcctg ctgtttgcct acgtgctgct catggatttc cattcggtgc cacacccccc 2340 
cgagctggtc ctgtactcgc tggtctttgt cctcttctgt gatgaagtga gacagtggta 2400 
cgtaaatggg gtgaattatt ttactgacct gtggaatgtg atggacacgc tggggctttt 2460 
ttacttcata gcaggaattg tatttcggct ccactcttct aataaaagct ctttgtattc 2520 
tggacgagtc attttctgtc tggactacat tattttcact ctaagattga tccacatttt 2580 
tactgtaagc agaaacttag gacccaagat tataatgctg cagaggatgc tgatcgatgt 2640 
gttcttcttc ctgttcctct ttgcggtgtg gatggtggcc tttggcgtgg ccaggcaagg 2700 
gatccttagg cagaatgagc agcgctggag gtggatattc cgttcggtca tctacgagcc 2760 
ctacctggcc atgttcggcc aggtgcccag tgacgtggat ggtaccacgt atgactttgc 2820 
ccactgcacc ttcactggga atgagtccaa gccactgtgt gtggagctgg atgagcacaa 2880 
cctgccccgg ttccccgagt ggatcaccat ccccctggtg tgcatctaca tgttatccac 2940 
caacatcctg ctggtcaacc tgctggtcgc catgtttggc tacacggtgg gcaccgtcca 3000 
ggagaacaat gaccaggtct ggaagttcca gaggtacttc ctggtgcagg agtactgcag 3060 
ccgcctcaat atccccttcc ccttcatcgt cttcgcttac ttctacatgg tggtgaagaa 3120 
gtgcttcaag tgttgctgca aggagaaaaa catggagtct tctgtctgct gtttcaaaaa 3180 
tgaagacaat gagactctgg catgggaggg tgtcatgaag gaaaactacc ttgtcaagat 3240 
caacacaaaa gccaacgaca cctcagagga aatgaggcat cgatttagac aactggatac 3300 
aaagcttaat gatctcaagg gtcttctgaa agagattgct aataaaatca aataaaactg 3360 
tatgaactct aatggagaaa aatctaatta tagcaagatc atattaagga atgctgatga 3420 
acaattttgc tatcgactac taaatgagag attttcagac ccctgggtac atggtggatg 3480 
attttaaatc accctagtgt gctgagacct tgagaataaa gtgtgtgatt ggtttcatac 3540 
ttgaagacgg atataaagga agaatatttc ctttatgtgt ttctccagaa tggtgcctgt 3600 
ttctctctgt gtctcaatgc ctgggactgg aggttgatag tttaagtgtg ttcttaccgc 3660 
ctcctttttc ctttaatctt atttttgatg aacacatata taggagaaca tctatcctat 3720 
gaataagaac ctggtcatgc tttactcctg tattgttatt ttgttcattt ccaattgatt 3780 
ctctactttt cccttttttg tattatgtga ctaattagtt ggcatattgt taaaagtctc 3840 
tcaaattagg ccagattcta aaacatgctg cagcaagagg accccgctct cttcaggaaa 3900 
agtgttttca tttctcagga tgcttcttac ctgtcagagg aggtgacaag gcagtctctt 3960 
gctctcttgg actcaccagg ctcctattga aggaaccacc cccattccta aatatgtgaa 4020 
aagtcgccca aaatgcaacc ttgaaaggca ctactgactt tgttcttatt ggatactcct 4080 
cttattattt ttccattaaa aataatagct ggctattata gaaaatttag accatacaga 4140 
gatgtagaaa gaacataaat tgtccccatt accttaaggt aatcactgct aacaatttct 4200 
ggatggtttt tcaagtctat tttttttcta tgtatgtctc aattctcttt caaaatttta 4260 
cagaatgtta tcatactaca tatatacttt ttatgtaagc tttttcactt agtattttat 4320 
caaatatgtt tttattatat tcatagcctt cttaaacatt atatcaataa ttgcataata 4380 
ggcaacctct agcgattacc ataattttgc tcattgaagg ctatctccag ttgatcattg 4440 
ggatgagcat ctttgtgcat gaatcctatt gctgtatttg ggaaaatttt ccaaggttag 4500 
attccaataa atatctattt attattaaat attaaaatat ctatttatta ttaaaaccat 4560 
ttataaggct ttttcataaa tgtatagcaa ataggaatta ttaacttgag cataagatat 4620 
gagatacatg aacctgaact attaaaataa aatattatat ttaaccctta gtttaagaag 4680 
aagtcaatat gcttatttaa atattatgga tggtgggcag atcacttgag gtcaggagtt 4740 
cgagaccagc ctggccaaca tggcaaaacc acatctctac taaaaataaa aaaattagct 4800 
gggtgtggtg gtgcactcct gtaatcccag ctactcagaa ggctgaggta caagaattgc 4860 
tggaacctgg gaggcggagg ttgcagtgaa ccaagattgc accactgcac tccagccggg 4920 
gtgacagagt gagactccga ctgaaaataa ataaataaat aaataaataa ataaataaat 4980 
attatggatg gtgaagggaa tggtatagaa ttggagagat tatcttactg aacacctgta 5040 
gtcccagctt tctctggaag tggtcgtatt tgagcaggat gtgcacaagg caattgaaat 5100 
gcccataatt agtttctcag ctttgaatac actataaact cactggctga aggaggaaat 5160 
tttagaagga agctactaaa agatctaatt tgaaaaacta caaaagcatt aactaaaaaa 5220 
gtttattttc cttttgtctg ggcagtagtg aaaataacta ctcacaacat tcactatgtt 5280 
tgcaaggaat taacacaaat aaaagatgcc tttttactta aacaccaaga cagaaaactt 5340 
gcccaatact gagaagcaac ttgcattaga gagggaactg ttaaatgttt tcaacccagt 5400 
tcatctggtg gatgtttttg caggttactc tgagaatttt gcttatgaaa aatcattatt 5460 
tttagtgtag ttcacaataa tgtattgaac atacttctaa tcaaaggtgc tatgtccttg 5520 
tgtatggtac taaatgtgtc ctgtgtactt ttgcacaact gagaatcctg cagcttggtt 5580 
taatgagtgt gttcatgaaa taaataatgg aggaattgtc a                     5621 

<210> 2 


<211> 1104 


<212> PRT 


<213> Homo sapiens 


<400> 2 


Met Ser Phe Arg Ala Ala Arg Leu Ser Met Arg Asn Arg Arg Asn Asp 

Thr Leu Asp Ser Thr Arg Thr Leu Tyr Ser Ser Ala Ser Arg Ser Thr 

Asp Leu Ser Tyr Ser Glu Ser Asp Leu Val Asn Phe Ile Gln Ala Asn 

Phe Lys Lys Arg Glu Cys Val Phe Phe Thr Lys Asp Ser Lys Ala Thr 
  
Glu Asn Val Cys Lys Cys Gly Tyr Ala Gln Ser Gln His Met Glu Gly 

Thr Gln Ile Asn Gln Ser Glu Lys Trp Asn Tyr Lys Lys His Thr Lys 

Glu Phe Pro Thr Asp Ala Phe Gly Asp Ile Gln Phe Glu Thr Leu Gly 
	
Lys Lys Gly Lys Tyr Ile Arg Leu Ser Cys Asp Thr Asp Ala Glu Ile 

Leu Tyr Glu Leu Leu Thr Gln His Trp His Leu Lys Thr Pro Asn Leu 
    
Val Ile Ser Val Thr Gly Gly Ala Lys Asn Phe Ala Leu Lys Pro Arg 

Met Arg Lys Ile Phe Ser Arg Leu Ile Tyr Ile Ala Gln Ser Lys Gly 
		
Ala Trp Ile Leu Thr Gly Gly Thr His Tyr Gly Leu Met Lys Tyr Ile 
	   
Gly Glu Val Val Arg Asp Asn Thr Ile Ser Arg Ser Ser Glu Glu Asn 
	
Ile Val Ala Ile Gly Ile Ala Ala Trp Gly Met Val Ser Asn Arg Asp 
    
Thr Leu Ile Arg Asn Cys Asp Ala Glu Gly Tyr Phe Leu Ala Gln Tyr 

Leu Met Asp Asp Phe Thr Arg Asp Pro Leu Tyr Ile Leu Asp Asn Asn 
		
His Thr His Leu Leu Leu Val Asp Asn Gly Cys His Gly His Pro Thr 
	  
Val Glu Ala Lys Leu Arg Asn Gln Leu Glu Lys Tyr Ile Ser Glu Arg 
	
Thr Ile Gln Asp Ser Asn Tyr Gly Gly Lys Ile Pro Ile Val Cys Phe 
 
Ala Gln Gly Gly Gly Lys Glu Thr Leu Lys Ala Ile Asn Thr Ser Ile 

Lys Asn Lys Ile Pro Cys Val Val Val Glu Gly Ser Gly Gln Ile Ala 
		
Asp Val Ile Ala Ser Leu Val Glu Val Glu Asp Ala Leu Thr Ser Ser 
	 
Ala Val Lys Glu Lys Leu Val Arg Phe Leu Pro Arg Thr Val Ser Arg 

Leu Pro Glu Glu Glu Thr Glu Ser Trp Ile Lys Trp Leu Lys Glu Ile 
   
Leu Glu Cys Ser His Leu Leu Thr Val Ile Lys Met Glu Glu Ala Gly 

Asp Glu Ile Val Ser Asn Ala Ile Ser Tyr Ala Leu Tyr Lys Ala Phe 
		
Ser Thr Ser Glu Gln Asp Lys Asp Asn Trp Asn Gly Gln Leu Lys Leu 
	   
Leu Leu Glu Trp Asn Gln Leu Asp Leu Ala Asn Asp Glu Ile Phe Thr 
	
Asn Asp Arg Arg Trp Glu Ser Ala Asp Leu Gln Glu Val Met Phe Thr 
   
Ala Leu Ile Lys Asp Arg Pro Lys Phe Val Arg Leu Phe Leu Glu Asn 

Gly Leu Asn Leu Arg Lys Phe Leu Thr His Asp Val Leu Thr Glu Leu 
		
Phe Ser Asn His Phe Ser Thr Leu Val Tyr Arg Asn Leu Gln Ile Ala 
	  
Lys Asn Ser Tyr Asn Asp Ala Leu Leu Thr Phe Val Trp Lys Leu Val 

Ala Asn Phe Arg Arg Gly Phe Arg Lys Glu Asp Arg Asn Gly Arg Asp 
   
Glu Met Asp Ile Glu Leu His Asp Val Ser Pro Ile Thr Arg His Pro 

Leu Gln Ala Leu Phe Ile Trp Ala Ile Leu Gln Asn Lys Lys Glu Leu 

Ser Lys Val Ile Trp Glu Gln Thr Arg Gly Cys Thr Leu Ala Ala Leu 
	   
Gly Ala Ser Lys Leu Leu Lys Thr Leu Ala Lys Val Lys Asn Asp Ile 
	
Asn Ala Ala Gly Glu Ser Glu Glu Leu Ala Asn Glu Tyr Glu Thr Arg 
  
Ala Val Glu Leu Phe Thr Glu Cys Tyr Ser Ser Asp Glu Asp Leu Ala 

Glu Gln Leu Leu Val Tyr Ser Cys Glu Ala Trp Gly Gly Ser Asn Cys 
	
Leu Glu Leu Ala Val Glu Ala Thr Asp Gln His Phe Ile Ala Gln Pro 
	
Gly Val Gln Asn Phe Leu Ser Lys Gln Trp Tyr Gly Glu Ile Ser Arg 
	
Asp Thr Lys Asn Trp Lys Ile Ile Leu Cys Leu Phe Ile Ile Pro Leu 
   
Val Gly Cys Gly Phe Val Ser Phe Arg Lys Lys Pro Val Asp Lys His 

Lys Lys Leu Leu Trp Tyr Tyr Val Ala Phe Phe Thr Ser Pro Phe Val 
	
Val Phe Ser Trp Asn Val Val Phe Tyr Ile Ala Phe Leu Leu Leu Phe 
	 
Ala Tyr Val Leu Leu Met Asp Phe His Ser Val Pro His Pro Pro Glu 
	
Leu Val Leu Tyr Ser Leu Val Phe Val Leu Phe Cys Asp Glu Val Arg 
  
Gln Trp Tyr Val Asn Gly Val Asn Tyr Phe Thr Asp Leu Trp Asn Val 

Met Asp Thr Leu Gly Leu Phe Tyr Phe Ile Ala Gly Ile Val Phe Arg 

Leu His Ser Ser Asn Lys Ser Ser Leu Tyr Ser Gly Arg Val Ile Phe 
	
Cys Leu Asp Tyr Ile Ile Phe Thr Leu Arg Leu Ile His Ile Phe Thr 
	
Val Ser Arg Asn Leu Gly Pro Lys Ile Ile Met Leu Gln Arg Met Leu 
   
Ile Asp Val Phe Phe Phe Leu Phe Leu Phe Ala Val Trp Met Val Ala 

Phe Gly Val Ala Arg Gln Gly Ile Leu Arg Gln Asn Glu Gln Arg Trp 

Arg Trp Ile Phe Arg Ser Val Ile Tyr Glu Pro Tyr Leu Ala Met Phe 

Gly Gln Val Pro Ser Asp Val Asp Gly Thr Thr Tyr Asp Phe Ala His 

Cys Thr Phe Thr Gly Asn Glu Ser Lys Pro Leu Cys Val Glu Leu Asp 
 
Glu His Asn Leu Pro Arg Phe Pro Glu Trp Ile Thr Ile Pro Leu Val 

Cys Ile Tyr Met Leu Ser Thr Asn Ile Leu Leu Val Asn Leu Leu Val 

Ala Met Phe Gly Tyr Thr Val Gly Thr Val Gln Glu Asn Asn Asp Gln 

Val Trp Lys Phe Gln Arg Tyr Phe Leu Val Gln Glu Tyr Cys Ser Arg 

Leu Asn Ile Pro Phe Pro Phe Ile Val Phe Ala Tyr Phe Tyr Met 

Val Val Lys Lys Cys Phe Lys Cys Cys Cys Lys Glu Lys Asn Met 
  
Glu Ser Ser Val Cys Cys Phe Lys Asn Glu Asp Asn Glu Thr Leu 
    
Ala Trp Glu Gly Val Met Lys Glu Asn Tyr Leu Val Lys Ile Asn 
  
Thr Lys Ala Asn Asp Thr Ser Glu Glu Met Arg His Arg Phe Arg 
   
Gln Leu Asp Thr Lys Leu Asn Asp Leu Lys Gly Leu Leu Lys Glu 

Ile Ala Asn Lys Ile Lys 
