Peptides, methods for assaying human pepsinogen I or human pepsin I and assay kits

Abstract

Peptides of the formula (I) R-X-ProlleGlu-W-Y-Z  (I) (wherein R is hydrogen, an amino-protective group, residue carrying one or two D- or L-amino acid, X is Lys or Arg, W is Phe orPhe(NO 2 ) (in which Phe(NO 2 ) is p-nitrophenylalanine.), Y is Phe, Phe(NO 2 ), Tyr, 3,5-diiodotyrosine, norleucine, Leu, Asp(OBzl) or Met (in which OBzl is benzyloxy.), Z is an aniline, aminocoumarin or aminonaphthalene derivative residue.), or acid addition salts thereof. Peptides of the formula (I) are specific substrates for human pepsin I, so they are used in assaying human pepsin I or human pepsinogen I. These peptide are useful in the diagnosis of gastric diseases such as gastric cancer and gastric ulcer.

What is claimed is  
     
         1 . A peptide of the formula (I)  
       R-X-ProlleGlu-W-Y-Z  (I) 
       (wherein R is hydrogen, an amino-protective group, or a residue containing one or two D-amino acid orL-amino acid, 
 X is Lys or Arg residue,  
 W is Phe or Phe(NO 2 ) residue (in which Phe(NO 2 ) is p-nitrophenylalanine residue.),  
 Y is Phe, Phe(NO 2 ), Tyr, Dit, Nle, Leu, Asp(OBzl) or Met residue (in which Dit is 3,5-diiodotyrosine residue, Nle is norleucine residue, OBzl is benzyloxy and Phe(NO 2 ) is as defined hereinbefore.), and  
 Z is an aniline derivative residue, an aminocoumarine derivative residue or an aminonaphthalene derivative residue.), or an acid addition salt thereof.  
 
     
     
         2 . A peptide according to  claim 1  in which Y is Phe, Phe(NO 2 ), Tyr or Nle residue wherein all the symbols are as defined in  claim 1 .  
     
     
         3 . A peptide according to  claim 1  or  2  in which R is hydrogen or C1˜6 alkylcarbonyl.  
     
     
         4 . A peptide of the formula (Ia)  
       N α -Ac-LysProlleGluPheNle-pNA  (Ia) 
       (wherein Ac is acetyl, Nle is norleucine residue and pNA is p-nitroaniline residue.), 
 a peptide of the formula (Ib)  
 LysProlleGluPheNle-pNA  (Ib) 
 (wherein all the symbols are as defined hereinbefore.  
 a peptide of the formula (Ic)  
 LysProIleGluPheTyr-pNA  (lC) 
 (wherein all the symbols are as defined hereinbefore.  
 a peptide of the formula (Id)  
 LysProlleGluPhePhe-pNA  (Id) 
 (wherein all the symbols are as defined hereinbefore.  
 a peptide of the formula (Ie)  
 LysProlleGluPhePhe(NO2)-pNA  (Ie) 
 (wherein Phe(NO 2 ) is p-nitro-phenylalanine residue and the other symbols are as defined hereinbefore.  
 or a peptide of the formula (If)  
 N α -Ac-LysProIleGluPhe(NO 2 )Nle-pNA  (If) 
 (wherein all the symbols are as defined hereinbefore. or acid addition salts thereof.  
 
     
     
         5 . A method for assaying human pepsinogen I or human pepsin I characterized by 
 digesting a peptide of the formula (I) depicted in  claim 1  (wherein all the symbols are as defined in claim  1 ) or an acid addition salt thereof by human pepsin I which is obtained by activation of human pepsinogen I in a sample or human pepsin I in a sample to obtain an amino acid derivative of the formula (II)    H-Y-Z  (II)   (wherein all the symbols are as defined in claim  1 .)    digesting the obtained amino acid derivative of the formula (II) by aminopeptidase to obtain an aniline, aminocoumarine or aminonaphthalene derivative of the formula Z-H, and then detecting the obtained aniline, aminocoumarine or aminonaphthalene derivative.    
     
     
         6 . A method for assaying according to  claim 5  using a peptide of the formula (Ia), (Ib), (Ic), (Id), (Ie) or (If) depicted in  claim 4  (wherein all the symbols are as defined in claim  4 ) or an acid addition salt thereof .  
     
     
         7 . A kit for assaying human pepsinogen I or human pepsin I which is characterized by comprising a peptide of the formula (I) as depicted in  claim 1  (wherein all the symbols are as defined in claim  1 ) or an acid addition salt thereof as a substrate, and aminopeptidase.