Cyclic peptide formation catalyzed by an antibody ligase.

ABSTRACT: Cyclic hexapeptides represent a class of compounds with important, diverse biological activities. We report herein that the antibody 16G3 catalyzes the cyclization of d-Trp-Gly-Pal-Pro-Gly-Phe small middle dotp-nitrophenyl ester (8a) to give c-(d-Trp-Gly-Pal-Pro-Gly-l-Phe) (11a). The antibody does not, however, catalyze either epimerization or hydrolysis. The resulting rate enhancement of the cyclization by 16G3 (22-fold) was sufficient to form the desired product in greater than 90% yield. In absolute rate terms, the turnover of 16G3 is estimated to be 2 min(-1). The background rate of epimerization of 8a was reduced from 10 to 1% and hydrolysis from 50 to 4% in the presence of 16G3. As expected, the catalytic effects of 16G3 were blocked by the addition of an amount of the hapten equal t

SUBMITTER: Smithrud DB 

PROVIDER: S-EPMC15735 | biostudies-literature | 2000 Feb

REPOSITORIES: biostudies-literature