SGIP peptides

Abstract

The present invention is directed to polynucleotides, polypeptides, peptides, variants and uses thereof for novel peptide fragments which have homology to motilin. Tissue distribution of the mRNA for the novel polypeptide fragment is specific to the stomach, small intestine and pancreas. Binding of the peptide fragment has been shown in kidney and small intestine. The present invention further includes agonists, antagonists, variants, antibodies and host cells expressing the cDNA encoding the novel SGIP peptide.

1 . An isolated polypeptide molecule consisting of residues X through 9 as shown in SEQ ID NO:6, wherein X is an integer from 1 to 4, inclusive, and wherein at least Y of said residues are as in the corresponding region as shown in SEQ ID NO:2, wherein Y is 9 minus X.  
     
     
         2 . An isolated polypeptide molecule consisting of residues X through 10 as shown in SEQ ID NO:6, wherein X is an integer from 2 to 4, inclusive, and wherein at least 10 minus X residues are as in the corresponding region as shown in SEQ ID NO:2.  
     
     
         3 . An isolated polypeptide molecule consisting of residues X through 11 as shown in SEQ ID NO:6, wherein X is 3 or 4, inclusive, and at least 11 minus X residues are as in the corresponding region as shown in SEQ ID NO:2.  
     
     
         4 . An isolated polypeptide molecule selected from the group consisting of: 
 a) a polypeptide molecule consisting of residues 1 to 9 as shown in SEQ ID NO:2;    b) a polypeptide molecule consisting of residues 2 to 9 as shown in SEQ ID NO:2;    c) a polypeptide molecule consisting of residues 3 to 9 as shown in SEQ ID NO:2;    d) a polypeptide molecule consisting of residues 4 to 9 as shown in SEQ ID NO:2;    e) a polypeptide molecule consisting of residues 2 to 10 as shown in SEQ ID NO:2;    f) a polypeptide molecule consisting of residues 3 to 10 as shown in SEQ ID NO:2;    g) a polypeptide molecule consisting of residues 4 to 10 as shown in SEQ ID NO:2;    h) a polypeptide molecule consisting of residues 3 to 11 as shown in SEQ ID NO:2; and    i) a polypeptide molecule consisting of residues 4 to 11 as shown in SEQ ID NO:2;    wherein the polypeptide molecule has one amino acid substitution at residue X, wherein residue X is an integer from 1 to 11, inclusive, and wherein the amino acid is substituted with the corresponding amino acid at residue X as shown in SEQ ID NO:6.    
     
     
         5 . An isolated polypeptide molecule according to  claim 4 , wherein the polypeptide molecule consists of residues 1 to 9 as shown in SEQ ID NO:2.  
     
     
         6 . An isolated polypeptide molecule according to  claim 4 , wherein the polypeptide molecule consists of residues 2 to 9 as shown in SEQ ID NO:2.  
     
     
         7 . An isolated polypeptide molecule according to  claim 4 , wherein the polypeptide molecule consists of residues 3 to 9 as shown in SEQ ID NO:2.  
     
     
         8 . An isolated polypeptide molecule according to  claim 4 , wherein the polypeptide molecule consists of residues 4 to 9 as shown in SEQ ID NO:2.  
     
     
         9 . An isolated polypeptide molecule according to  claim 4 , wherein the polypeptide molecule consists of residues 2 to 10 as shown in SEQ ID NO:2.  
     
     
         10 . An isolated polypeptide molecule according to  claim 4 , wherein the polypeptide molecule consists of residues 3 to 10 as shown in SEQ ID NO:2.  
     
     
         11 . An isolated polypeptide molecule according to  claim 4 , wherein the polypeptide molecule consists of residues 4 to 10 as shown in SEQ ID NO:2.  
     
     
         12 . An isolated polypeptide molecule according to  claim 4 , wherein the polypeptide molecule consists of residues 3 to 11 as shown in SEQ ID NO:2.  
     
     
         13 . An isolated polypeptide molecule according to  claim 4 , wherein the polypeptide molecule consists of residues 4 to 11 as shown in SEQ ID NO:2.  
     
     
         14 . A method of modulating contractility in duodenum or jejunum tissue comprising administering the isolated polypeptide of  claim 4  to said tissue.  
     
     
         15 . A method of modulating pancreatic secretion of hormones and digestive enzymes comprising administering the isolated polypeptide of  claim 4  to a mammal.  
     
     
         16 . A method of inducing growth hormone secretion comprising administering the isolated polypeptide of  claim 4  to a mammal.  
     
     
         17 . A method of modulating gastric emptying comprising admisitering the isolated peptide of  claim 4  to a mammal.  
     
     
         18 . An isolated polypeptide molecule selected from the group consisting of: 
 a) a polypeptide molecule consisting of residues 1 to 9 as shown in SEQ ID NO:2;    b) a polypeptide molecule consisting of residues 2 to 9 as shown in SEQ ID NO:2;    c) a polypeptide molecule consisting of residues 3 to 9 as shown in SEQ ID NO:2;    d) a polypeptide molecule consisting of residues 4 to 9 as shown in SEQ ID NO:2;    e) a polypeptide molecule consisting of residues 2 to 10 as shown in SEQ ID NO:2;    f) a polypeptide molecule consisting of residues 3 to 10 as shown in SEQ ID NO:2;    g) a polypeptide molecule consisting of residues 4 to 10 as shown in SEQ ID NO:2;    h) a polypeptide molecule consisting of residues 3 to 11 as shown in SEQ ID NO:2; and    i) a polypeptide molecule consisting of residues 4 to 11 as shown in SEQ ID NO:2.    
     
     
         19 . An isolated polypeptide molecule according to  claim 18 , wherein the polypeptide molecule consists of residues 1 to 9 as shown in SEQ ID NO:2.  
     
     
         20 . An isolated polypeptide molecule according to  claim 18 , wherein the polypeptide molecule consists of residues 2 to 9 as shown in SEQ ID NO:2.  
     
     
         21 . An isolated polypeptide molecule according to  claim 18 , wherein the polypeptide molecule consists of residues 3 to 9 as shown in SEQ ID NO:2.  
     
     
         22 . An isolated polypeptide molecule according to  claim 18 , wherein the polypeptide molecule consists of residues 4 to 9 as shown in SEQ ID NO:2.  
     
     
         23 . An isolated polypeptide molecule according to  claim 18 , wherein the polypeptide molecule consists of residues 2 to 10 as shown in SEQ ID NO:2.  
     
     
         24 . An isolated polypeptide molecule according to  claim 18 , wherein the polypeptide molecule consists of residues 3 to 10 as shown in SEQ ID NO:2.  
     
     
         25 . An isolated polypeptide molecule according to  claim 18 , wherein the polypeptide molecule consists of residues 4 to 10 as shown in SEQ ID NO:2.  
     
     
         26 . An isolated polypeptide molecule according to  claim 18 , wherein the polypeptide molecule consists of residues 3 to 11 as shown in SEQ ID NO:2.  
     
     
         27 . An isolated polypeptide molecule according to  claim 18 , wherein the polypeptide molecule consists of residues 4 to 11 as shown in SEQ ID NO:2.  
     
     
         28 . A method of modulating contractility in duodenum or jejunum tissue comprising administering the isolated polypeptide of  claim 18  to said tissue.  
     
     
         29 . A method of modulating pancreatic secretion of hormones and digestive enzymes comprising administering the isolated polypeptide of  claim 18  to a mammal.  
     
     
         30 . A method of inducing growth hormone secretion comprising administering the isolated polypeptide of  claim 18  to a mammal.  
     
     
         31 . A method of modulating gastric emptying comprising administering the isolated polypeptide of  claim 18  to a mammal.  
     
     
         32 . An isolated polynucleotide molecule having a polynucleotide sequence selected from the group consisting of: 
 a) a polynucleotide sequence as shown in SEQ ID NO:1;    b) a polynucleotide molecule that is complementary to the polynucleotide sequence as shown in SEQ ID NO:1; and    c) a polynucleotide sequence as shown in SEQ ID NO:7.    
     
     
         33 . A polynucleotide vector comprising the isolated polynucleotide molecule of  claim 32 , a transcription promoter, and a transcription terminator, wherein the promoter is operably linked with the nucleic acid molecule, and wherein the nucleic acid molecule is operably linked with the transcription terminator.  
     
     
         34 . An isolated polypeptide molecule consisting of an amino acid sequence selected from 
 a) residues 3 to 9 of SEQ ID NO:2;    b) residues 2 to 9 of SEQ ID NO:2;    c) residues 1 to 9 of SEQ ID NO:2;    d) residues 3 to 10 of SEQ ID NO:2;    e) residues 2 to 10 of SEQ ID NO:2; and    f) residues 3 to 11 of SEQ ID NO:2,    wherein the polypeptide molecule has one amino acid substitution.    
     
     
         35 . The isolated polypeptide molecule according to  claim 34 , wherein the amino acid substitution is selected from 
 a) the amino acid at position 1 of SEQ ID NO:2 is substituted with serine, alanine, threonine, or methionine;    b) the amino acid at position 2 of SEQ ID NO:2 is substituted with glycine, alanine, threonine, or methionine;    c) the amino acid at position 3 of SEQ ID NO:2 is substituted with glycine, alanine, threonine, or methionine;    d) the amino acid at position 4 of SEQ ID NO:2 is substituted with tryptophan, tyrosine, leucine, valine, or isoleucine;    e) the amino acid at position 5 of SEQ ID NO:2 is substituted with isoleucine, valine, phenylalanine, or tyrosine;    f) the amino acid at position 6 of SEQ ID NO:2 is substituted with glycine, alanine, threonine, methionine, or proline;    g) the amino acid at position 7 of SEQ ID NO:2 is substituted with alanine, glycine, isoleucine, leucine, or valine;    h) the amino acid at position 8 of SEQ ID NO:2 is substituted with aspartic acid;    i) the amino acid at position 9 of SEQ ID NO:2 is substituted with arginine, lysine, phenylalanine, or tyrosine;    j) the amino acid at position 10 of SEQ ID NO:2 is substituted with asparagine, serine, threionine, histidine, alanine, glutamic acid, aspartic acid, lysine, or arginine; or    k) the amino acid at position 11 of SEQ ID NO:2 is substituted with glutamine, asparagine, serine, threionine, histidine, or alanine.    
     
     
         36 . An isolated polypeptide molecule consisting of an amino acid sequence selected from 
 a) residues 4 to 9 of SEQ ID NO:2;    b) residues 4 to 10 of SEQ ID NO:2; and    c) residues 4 to 11 of SEQ ID NO:2,    wherein the polypeptide molecule has one amino acid substitution.    
     
     
         37 . The isolated polypeptide molecule according to  claim 36 , wherein the amino acid substitution is selected from 
 a) the amino acid at position 4 of SEQ ID NO:2 is substituted with tryptophan, tyrosine, leucine, valine, or isoleucine;    b) the amino acid at position 5 of SEQ ID NO:2 is substituted with isoleucine, valine, phenylalanine, or tyrosine;    c) the amino acid at position 6 of SEQ ID NO:2 is substituted with glycine, alanine, threonine, methionine, or proline;    d) the amino acid at position 7 of SEQ ID NO:2 is substituted with alanine, glycine, isoleucine, leucine, or valine;    e) the amino acid at position 8 of SEQ ID NO:2 is substituted with aspartic acid;    f) the amino acid at position 9 of SEQ ID NO:2 is substituted with arginine, lysine, phenylalanine, or tyrosine;    g) the amino acid at position 10 of SEQ ID NO:2 is substituted with asparagine, serine, threionine, histidine, alanine, glutamic acid, aspartic acid, lysine, or arginine; or    h) the amino acid at position 11 of SEQ ID NO:2 is substituted with glutamine, asparagine, serine, threionine, histidine, or alanine.