CHARACTERISTICS OF THE PEPTIDASE ACTIVITY CONTAINED IN TAIWAN COBRA (NAJA-NAJA-ATRA) VENOM

Cobra venoms (Naja species) contain a little-understood peptidase acti vity which shows specificity towards small peptides containing glycine and non-polar aromatic/aliphatic residues. We have examined the abili ty of whole cobra venom to degrade several types of peptide with empha sis on the action of Taiwan cobra (Naja naja atra) venom on L-alanylgl ycylglycine and glycylglycyl-L-phenylalanine. These are competing subs trates, and it proved possible to generate inhibitors of the degradati on of glycylglycyl-L-phenylalanine by synthesizing L-alanylglycylglyci ne analogues in which the peptide bond between the second and third re sidues had been replaced by different linkages. These analogues were t hemselves resistant to hydrolysis. The peptidase activity can also be inhibited by bestatin, captopril and chloromethyl ketones. Kinetic ana lyses suggested that even the best substrate discovered was of poor ef ficacy, so the natural peptide substrate remains to be identified. In unsuccessful attempts to devise a reliable chromogenic assay, it was f ound that the venom had activity against N-blocked amino acid p-nitrop henol esters, but not against leucine p-nitroanilide or ester substrat es for trypsin-like and chymotrypsin-like enzymes.