TY - JOUR
T1 - Specific inhibitory conformation of dipeptides for chymotrypsin
AU - Shimohigashi, Yasuyuki
AU - Ogawa, Tomohisa
AU - Kodama, Hiroaki
AU - Sakamoto, Hiroshi
AU - Yoshitomi, Haruko
AU - Waki, Michinori
AU - Ohno, Motonori
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 1990/2/14
Y1 - 1990/2/14
N2 - 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.
AB - 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.
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U2 - 10.1016/0006-291X(90)91031-M
DO - 10.1016/0006-291X(90)91031-M
M3 - Article
C2 - 2306257
AN - SCOPUS:0025015061
VL - 166
SP - 1460
EP - 1466
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -