Strong inhibitory effect of sugar-biphenylylboronic acid complexes on the hydrolytic activity of α-chymotrypsin

Hikaru Suenaga, Masafumi Mikami, Hiromasa Yamamoto, Takaaki Harada, Seiji Shinkai

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Boronic acids act as transition-state analogues for certain peptidases. The inhibitory effect of 2-, 3- and 4-biphenylylboronic acids (2a, 2b and 2c) on the hydrolytic activity of α-chymotrypsin has been investigated. These inhibitors were employed to monitor the binding event [formation of covalent bond with either serine residue (195) or histidine residue (57)] occurring in the active site by a fluorescence method. It was shown that the decrease in the fluorescence intensity, which is induced by the formation of a covalent bond with the boronic acid moiety, is well correlated with the inhibitory effect estimated by kinetic measurements. The inhibitory effect appeared in the order 2a < 2c ≪ 2b (Ki = 1.6 × 10-6 mol dm -3). Interestingly, the inhibitory effect was further intensified by added saccharides. In particular, the combined system of 2b and D-glucose strongly inhibited the enzyme reaction, the inhibitory effect (Ki = 1.1 × 10-7 mol dm-3) being stronger than that of a specific inhibitor, chymostatin (Ki = 4.8 × 10-7 mol dm-3). Hence, saccharides act as a 'co-inhibitor' in the boronic acid inhibition system. This is a novel and efficient inhibition system for α-chymotrypsin (and probably more generally for other peptidases).

Original languageEnglish
Pages (from-to)1733-1738
Number of pages6
JournalJournal of the Chemical Society, Perkin Transactions 1
Issue number13
Publication statusPublished - Dec 1 1995
Externally publishedYes

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Boronic Acids
Sugar Acids
Chymotrypsin
Covalent bonds
Peptide Hydrolases
Fluorescence
Histidine
Serine
Glucose
Kinetics
Acids
Enzymes

All Science Journal Classification (ASJC) codes

  • Chemistry(all)

Cite this

Strong inhibitory effect of sugar-biphenylylboronic acid complexes on the hydrolytic activity of α-chymotrypsin. / Suenaga, Hikaru; Mikami, Masafumi; Yamamoto, Hiromasa; Harada, Takaaki; Shinkai, Seiji.

In: Journal of the Chemical Society, Perkin Transactions 1, No. 13, 01.12.1995, p. 1733-1738.

Research output: Contribution to journalArticle

Suenaga, Hikaru ; Mikami, Masafumi ; Yamamoto, Hiromasa ; Harada, Takaaki ; Shinkai, Seiji. / Strong inhibitory effect of sugar-biphenylylboronic acid complexes on the hydrolytic activity of α-chymotrypsin. In: Journal of the Chemical Society, Perkin Transactions 1. 1995 ; No. 13. pp. 1733-1738.
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