Compounds and Methods for Inhibiting Axillary Malodour

Abstract

Enzymes mediating in the release of compounds characteristic of human malodour and in particular axillary malodour, and compounds that inhibit said enzymes having the general formula (I)

1 . An isolated N a -acyl-glutamine-aminoacylase. 
     
     
         2 . An enzyme comprising the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
         3 . An enzyme encoded for by nucleic acid comprising a nucleotide sequence set forth in SEQ ID NO: 5. 
     
     
         4 . An isolated nucleic acid encoding for an enzyme comprising the amino acid sequence of SEQ ID NO: 1. 
     
     
         5 . An isolated nucleic acid according to  claim 4  comprising a nucleotide sequence set forth in SEQ ID NO: 5. 
     
     
         6 . An expression vector comprising nucleic acid encoding for the amino acid sequence of SEQ ID NO: 1. 
     
     
         7 . An expression vector according to  claim 6  comprising nucleic acid comprising a nucleotide sequence set forth in SEQ ID NO: 5. 
     
     
         8 . Host cells transformed with expression vectors according to  claim 6  or  claim 7 . 
     
     
         9 . A method for the production of an enzyme as defined in any of the  claims 1  to  3  which comprises culturing a host cell having incorporated therein an expression vector encoding for the enzyme, under conditions sufficient for expression of said enzyme in said host cell, thereby causing the production of an expressed enzyme; and recovering the enzyme produced by the cell. 
     
     
         10 . Compounds of formula (I). 
       
         
           
           
               
               
           
         
         wherein 
         Y represents a direct bond to X, or a divalent chain that may contain carbon, oxygen or nitrogen atoms, 
         X is a zinc-chelating group, and 
         R 1  is a linear, branched or cyclic carbon chain having about 1 to 14 carbon atoms, optionally containing one or more heteroatoms such as O, N or S, or unsaturation, the chain optionally supports one or more substituents selected from amide, ester, keto, ether, amine, halogen or hydroxyl, or aryl or heteroaryl groups, which aryl or heteroaryl groups optionally support one or more substituents selected from amide, ester, keto, ether, amine, halogen, alkyl or hydroxyl. 
       
     
     
         11 . Compound according to  claim 10  wherein Y is an amide group —CONH—, an alkylene group selected from methylene, ethylene or propylene, —CH 2 —NH—, or —NH—. 
     
     
         12 . Compound according to  claim 10  or  claim 11  wherein X is a methylene thiol group (II), a phosphinyl group (III), or a group bearing a carboxylic acid group. 
     
     
         13 . Compound according to any of the  claims 10  to  12  wherein the group R 1  is selected from n-butyl, sec-butyl, benzyl or phenylethyl. 
     
     
         14 . Compound according to  claims 10  to  13  wherein
 Y represents an amide group —CONH— when X is methylene thiol (II), or   Y represents a methylene group when X is phosphinyl (III).   
     
     
         15 . Inhibitor of an enzyme as defined in  claims 1  to  3  selected from a compound as defined in any of the  claims 10  to  14 . 
     
     
         16 . Composition comprising a body odour-suppressing quantity of a compound as defined in any of the  claims 10  to  15 . 
     
     
         17 . Composition according to  claim 16  wherein the compound is present in amounts of about 0.01 to 0.5% by weight. 
     
     
         18 . Composition according to  claim 16  or  claim 17  selected from cosmetic and personal care products, in particular deo-sticks, roll-ons, pump-sprays, aerosols, deodorant soaps, powders, solutions, gels, creams, sticks, balms and lotions. 
     
     
         19 . Use of a compounds or compositions according to any of the  claims 10  to  18  to inhibit the enzyme defined by any of the  claims 1  to  3  in its ability to cleave compounds contained in sweat into short-chained, branched fatty acids. 
     
     
         20 . A method of screening compounds for inhibitor activity of an enzyme as defined in any of the  claims 1  to  3  comprising the steps of I) incubating an enzyme or cell extract containing enzyme with a substrate and a compound with potential inhibitory properties, and II) measuring release of malodorous compounds and/or free L-glutamine. 
     
     
         21 . A method of suppressing axillary malodour comprising the step of providing a composition for application to a person in need of treatment, said composition containing an inhibitor compound and a dermatologically acceptable vehicle therefor, said compound being selected from a screening of compounds for activity in the inhibition of the enzyme.