论文部分内容阅读
别构调节(allosteric regulation)是指调节分子结合在正位活性位点(orthosteric site)以外的位点,诱导蛋白构象变化来调节蛋白活性位点功能。别构调节具有位点多样化、调节分子多元化、调节特异性高和调节效应有上限等优点,使其成为新兴药物开发的重要策略。已有很多研究人员针对现有靶点研发别构药物,与以往正位活性位点的竞争性药物相比,别构药物特异性更好,能够区分家族内的同源蛋白,副作用小,并且实现从别构位点至活性位点的远程通讯,能够和内源性配体同时结合靶蛋白协同发挥功能等优点。该文将从别构调节的发展历史、机制、研究方法、别构调节剂的研究进展及别构药物开发的未来展望作一简要综述。
Allosteric regulation refers to the regulation of the binding of molecules to sites other than the orthosteric site to induce conformational changes in the protein that regulate the activity of the protein’s active site. Allomorphism has the advantages of diversification of sites, diversification of regulatory molecules, high specificity of regulation and upper limit of regulatory effects, making it an important strategy for the development of emerging drugs. A number of researchers have developed targeted drugs for allogeneic drugs. Compared with competing active drugs in the ortho-active sites, allosteric drugs have better specificity and can distinguish homologous proteins in the family with less side effects. Realizing remote communication from allosteric sites to active sites can combine with endogenous ligands and target proteins to work synergistically. This article will give a brief review of the history, mechanism, research methods, development of allosteric modulators and the future development of allogeneic drug development.