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寄生虫学中的合理药物设计:以转唾液酸酶作为恰加斯病的案例研究

Rational drug design in parasitology: trans-sialidase as a case study for Chagas disease.

作者信息

Neres João, Bryce Richard A, Douglas Kenneth T

机构信息

Center for Drug Design, University of Minnesota, 516 Delaware Street SE, Minneapolis, MN 55455, USA.

出版信息

Drug Discov Today. 2008 Feb;13(3-4):110-7. doi: 10.1016/j.drudis.2007.12.004.

Abstract

Trypanosoma cruzi trans-sialidase is a potential target for Chagas disease chemotherapy. From the specific need of T. cruzi to obtain sialic acid through trans-sialidase-mediated transfers from host sources and the lack of alternative to this for the parasite, a good case can be made for T. cruzi trans-sialidase to serve as a potential drug target against Chagas disease. This review deals with both the particular aspects relevant to T. cruzi trans-sialidase as a target and generalises the situation for drug design in its broader aspects on the basis of some special problems in terms of rational drug design that T. cruzi trans-sialidase raises, particularly those of multiple gene copies and active site plasticity.

摘要

克氏锥虫转唾液酸酶是恰加斯病化疗的潜在靶点。鉴于克氏锥虫通过转唾液酸酶介导从宿主来源获取唾液酸的特殊需求,且该寄生虫没有其他替代途径,因此有充分理由认为克氏锥虫转唾液酸酶可作为抗恰加斯病的潜在药物靶点。本综述既探讨了与克氏锥虫转唾液酸酶作为靶点相关的特定方面,又基于克氏锥虫转唾液酸酶在合理药物设计方面引发的一些特殊问题,特别是多基因拷贝和活性位点可塑性问题,从更广泛的角度对药物设计的情况进行了概括。

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