Specific inhibitory conformation of dipeptides for chymotrypsin

Yasuyuki Shimohigashi, Tomohisa Ogawa, Hiroaki Kodama, Hiroshi Sakamoto, Haruko Yoshitomi, Michinori Waki, Motonori Ohno

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Based on the analyzed conformation of a chymotrypsin inhibitor H-{down triangle, open}Phe-Phe-OMe, we have designed a series of diastereomeric phenylalanylphenylalanine methyl esters and derivatives as possible inhibitors. Among the peptides synthesized, H-D-Phe-L-Phe-OMe was found to be very resistant to chymotrypsin in spite of its L-Phe-OMe structure at the C-terminus. It inhibited the enzyme fairly strongly and competitively with Ki = 9.0 × 10-5 M in the assay using Ac-Tyr-OEt as a substrate. The measurements of the NOEs in high-resolution 1H-NMR analyses indicated the presence of the hydrophobic core built by the intramolecular interaction between the D-Phe-phenyl and ester-methyl groups. It was suggested that this core interacts with the chymotrypsin S2 site (Trp215) and Phe2 with the S1 site. The backbone structure of this dipeptide was assumed to be in an inhibitory conformation that fits the active center of the enzyme.

Original languageEnglish
Pages (from-to)1460-1466
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number3
Publication statusPublished - 1990 Feb 14


Dive into the research topics of 'Specific inhibitory conformation of dipeptides for chymotrypsin'. Together they form a unique fingerprint.

Cite this