Bivalent inhibition of beta-tryptase: distance scan of neighboring subunits by dibasic inhibitors.
Bivalent inhibition of beta-tryptase: distance scan of neighboring subunits by dibasic inhibitors.
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β-类胰蛋白酶的二价抑制：二元抑制剂对邻近亚基的距离扫描。
DOI：
10.1016/s0960-894x(02)00063-x
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发表时间：
2002
影响因子：
2.7
通讯作者：
C. Sommerhoff
中科院分区：
文献类型：
--
作者：
N. Schaschke;A. Dominik;G. Matschiner;C. Sommerhoff
基于双功能二酮哌嗪为模板和间氨甲基苯丙氨酸精氨酸模拟物，我们合成了一类新的结构相关的二元类胰蛋白酶抑制剂与系统地增加间隔长度。这些化合物用于扫描β-类胰蛋白酶四聚体的两个相邻亚基的活性位点之间的距离。所获得的Ki值是末端氨基之间的距离的函数，并且表明氨基之间具有29-31个键的抑制剂的最佳结合。这些实验数据是在一个新的建模程序，允许对接的二价配体与来自预测完全一致。
Based on bifunctional diketopiperazines as templates and m-aminomethyl-phenylalanine as arginine mimetic, we have synthesized a new class of structurally related dibasic tryptase inhibitors with systematically increasing spacer length. These compounds were used to scan the distance between the active sites of two neighboring subunits of the β-tryptase tetramer. The Ki-values obtained are a function of the distance between the terminal amino groups and indicate optimal binding of inhibitors with 29–31 bonds between the amino groups. These experimental data are in full agreement with predictions derived from a novel modeling program that allows the docking of bivalent ligands.