Welcome to LookChem.com Sign In|Join Free

Article Doi

Chymotrypsin inhibitory conformation induced by amino acid side chain-side chain intramolecular CH/π interaction

DOI: 10.1039/P19960002479

Source and publish data:

Journal of the Chemical Society. Perkin transactions I p. 2479 - 2485 (1996)

Update date:2022-08-03

Topics:

Authors:

Shimohigashi, YasuyukiShimohigashi, Yasuyuki

Maeda, IoriMaeda, Iori

Nose, TakeruNose, Takeru

Ikesue, KoichiIkesue, Koichi

Sakamoto, HiroshiSakamoto, Hiroshi

Ogawa, TomohisaOgawa, Tomohisa

Ide, YuzuruIde, Yuzuru

Kawahara, MegumiKawahara, Megumi

Nezu, TakashiNezu, Takashi

Terada, YoshihiroTerada, Yoshihiro

Kawano, KeiichiKawano, Keiichi

Ohno, MotonoriOhno, Motonori

Read Full Text PDF DownLoad Join now for total 90,000,000 free articles

Article abstract of DOI:10.1039/P19960002479

Dipeptide amides H-D-Leu-Phe-NH-R have been found to assume a conformation induced by the CH/π interaction and to inhibit chymotrypsin strongly. A series of benzyl amide derivatives H-D-Leu-Phe-NH-[CH2]n-C6H5 (n = 0-4) have been assayed for chymotrypsin. They inhibit the enzyme in a competitive manner and the highest inhibition is achieved by the amide of n = 1 (Ki = 3.6 × 10-6 M). The activity enhancement is dependent upon the length of methylene chain, not upon the increase in molecular hydrophobicity, indicating the presence of an optimal distance between dipeptide backbone and C-terminal phenyl group for chymotrypsin inhibition. The C-terminal phenyl group has been found to interact with chymotrypsin stereospecifically. The R-isomer of H-D-Leu-Phe-NH-CH(CH3)-C6H5 is as active as the benzyl amide, while the S-isomer is about twenty-fold less active. When the fluorine atom is introduced at a para-position of the C-terminal phenyl group, the resulting dipeptide H-D-Leu-Phe-NH-CH2-C6H4F-p exhibits about six-times increased inhibitory activity (Ki = 6.1 × 107 M; this dipeptide is one of the most potent chymotrypsin inhibitors to date). 1H NMR conformational analyses of these dipeptide amide derivatives show the CH/π interaction between D-Leu-isobutyl and Phe-phenyl as a key structural element for chymotrypsin inhibition. These structural examinations strongly suggest that in the inhibitory conformation the C-terminal phenyl group fits the chymotrypsin S1 site, while the hydrophobic core constructed by D-Leu-Phe CH/π interaction fits the chymotrypsin S2 or S1′ site.

View More

Products guided by the article

Product name:(S)-2-Amino-3-phenyl-N-(4-phenyl-butyl)-propionamide

Cas No:35374-00-6

35374-00-6

R&D Labs maybe for 35374-00-6

Relevant to this article

Hot Product