席夫碱铜（II）和铁（III）螯合物在胰蛋白酶位点特异性切割中的应用。

Application of Schiff base copper(II) and iron(III) chelates to site-specific cleavage of a trypsin.

作者信息

Toyota E, Miyazaki H, Itoh K, Sekizaki H, Tanizawa K

机构信息

Faculty of Pharmaceutical Sciences, Health Science University of Hokkaido, Japan.

出版信息

Chem Pharm Bull (Tokyo). 1999 Jan;47(1):116-9. doi: 10.1248/cpb.47.116.

DOI:10.1248/cpb.47.116

PMID:9987832

Abstract

Amidine-containing Schiff base iron(III) and copper(II) chelates were prepared from alpha-amino acid, metal ion, and salicylaldehyde. These chelates behaved as specific inhibitors of trypsin, with Ki values in the range 10(-5)-10(-6) M. Selective cleavage of the trypsin backbone resulting from specific binding of the chelate to the trypsin active site was investigated. Cleavage was observed when trypsin was incubated with amidine-containing copper(II) or iron(III) chelate, H2O2, and ascorbate. Examination of the three-dimensional structure of trypsin suggests that cleavage occurred at a peptide bond within the Gly195-Ala204 sequence.

摘要

含脒基的席夫碱铁（III）和铜（II）螯合物由α-氨基酸、金属离子和水杨醛制备而成。这些螯合物表现为胰蛋白酶的特异性抑制剂，其抑制常数（Ki）值在10⁻⁵ - 10⁻⁶ M范围内。研究了螯合物与胰蛋白酶活性位点特异性结合导致的胰蛋白酶主链的选择性裂解。当胰蛋白酶与含脒基的铜（II）或铁（III）螯合物、过氧化氢和抗坏血酸一起孵育时，观察到了裂解现象。对胰蛋白酶三维结构的研究表明，裂解发生在甘氨酸195 - 丙氨酸204序列内的一个肽键处。