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ID: ALA1135257

Journal: Bioorg Med Chem Lett

Title: Bivalent inhibition of beta-tryptase: distance scan of neighboring subunits by dibasic inhibitors.

Authors: Schaschke N, Dominik A, Matschiner G, Sommerhoff CP.

Abstract: 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 beta-tryptase tetramer. The K(i)-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.

CiteXplore: 11959009

DOI: 10.1016/s0960-894x(02)00063-x