Kazmierski Wieslaw M, Boone Larry, Lawrence Wendell, Watson Chris, Kenakin Terry
Department of Medicinal Chemistry, GlaxoSmithKline Research and Development, 5 Moore Drive, Research Triangle Park, NC 27709, USA.
Curr Drug Targets Infect Disord. 2002 Sep;2(3):265-78. doi: 10.2174/1568005023342489.
With the discovery that CCR5 is the critical protein required for infection by M-tropic HIV, has come huge research efforts, both in academia and industry, to try to exploit this finding. Thus, research advances in the fields of virology, structural protein chemistry, and receptor pharmacology have combined to add a new understanding to the process of HIV fusion and possible mechanisms to prevent HIV entry. This review will approach this field from a receptor pharmacology viewpoint and outline some concepts of receptor allosterism and protein-protein interaction which may be relevant to CCR5 blockade. Many of these ideas may be explored in a practical sense with the advent of new small molecule CCR5 inhibitors currently entering the clinic.
随着发现CCR5是M型嗜亲性HIV感染所需的关键蛋白，学术界和工业界都付出了巨大的研究努力来尝试利用这一发现。因此，病毒学、结构蛋白化学和受体药理学领域的研究进展相结合，为HIV融合过程和预防HIV进入的可能机制增添了新的认识。本综述将从受体药理学的角度探讨这一领域，并概述一些可能与CCR5阻断相关的受体别构和蛋白质-蛋白质相互作用的概念。随着目前进入临床的新型小分子CCR5抑制剂的出现，其中许多想法可以在实际中进行探索。
