Inactivation of trypsin-like proteases by depsipeptides of p-guanidinobenzoic acid

Journal Article · Thu Jan 01 00:00:00 EST 1981 · J. Med. Chem.; (United States)

DOI:https://doi.org/10.1021/jm00138a011· OSTI ID:5212290

Ganu, V S; Shaw, E

A number of esters of p-guanidinobenzoic acid have been synthesized which contain a clycolyl peptide as the departing group. In the case of several enzymes such as trypsin and plasma kallikrein, depsipeptides were obtained which were considerably more reactive than the ethyl ester in inactivation of the protease by acyl-enzyme formation; the depsipeptide possessing -CH/sub 2/CO-Phe-NH/sub 2/ as a leaving group displayed the highest reactivity. They were less effective in the case of urokinase, plasmin, and urinary kallikrein.Boar acrosin was very susceptible to inactivation by both ethyl and peptidyl esters. Depsipeptides possessing a longer peptide chain and a secondary carbon as a leaving group showed lower activities. The results demonstrate the productive use of the departing group region of protease active centers to obtain selectivity.

• Research Organization: Brookhaven National Lab., Upton, NY
• OSTI ID: 5212290
• Journal Information: J. Med. Chem.; (United States), Vol. 24:6
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ENZYMES
COMPLEXES
KETONES
PEPTIDES
BIOCHEMICAL REACTION KINETICS
ACYLATION
AFFINITY
BENZOIC ACID
GUANIDINES
INACTIVATION
SUBSTRATES
CARBONIC ACID DERIVATIVES
CARBOXYLIC ACIDS
CHEMICAL REACTIONS
KINETICS
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PROTEINS
REACTION KINETICS
550200* - Biochemistry