| abstract |
The enzyme chymotrypsin has many biological functions. It would be useful to inhibit this enzyme for diagnostic and therapeutic purposes. However it is a nuisance to synthesise because it contains the amino acid capreomycidine. The present invention provides peptides which are alternative inhibitors of chymotrypsin and are more readily synthesised than chymostatin. The peptides of the invention are compounds of formula (Org). CO. (BAA). (NAA). X' (al), wherein: Org represents an organic residue, preferably a hydrocarbyl or oxyhydrocarbyl group; BAA represents the residue of a basic acyclic or aromatic amino acid which imparts to the amino acid a pKa of from about 10.5 to about 12.5 and is preferably a lysine, arginine or ornithine residue; NAA represents the residue of a neutral amino acid (being one with no charged side-chain) and is preferably leucine, valine, isoleucine or phenylalanine; X' (al) represents a phenylalanine, tyrosine or tryptophan residue in which the terminal carboxyl group has been replaced by an aldehyde group, and the stereochemical configuration of at least the X' group, and preferably throughout, is of the L-amino acid; derivatives thereof having a functionally equivalent derivative of the aldehyde group, in place of the aldehyde group and the acid addition salts of any of these compounds. The peptides can be synthesised by simple conventional methods. They are useful for diagnosis of chymotrypsin and for therapy, e.g. in treatment of muscular dystrophy. |