Debnath Asim K
Laboratory of Molecular Modeling & Drug Design, Lindsley F. Kimball Research Institute of The New York Blood Centre, 310 East 67th Street, New York, NY 10021, USA.
Expert Opin Investig Drugs. 2006 May;15(5):465-78. doi: 10.1517/13543784.15.5.465.
During the last decade, a great number of activities have been geared in identifying newer targets for inhibiting HIV infection as well as understanding the targets for already identified anti-HIV-1 agents. The success in converting a proof-of-concept peptide T-20 (previously named DP-178), from the C-terminal heptad repeat (CHR) region of the envelope glycoprotein gp41 of HIV-1, to a drug named enfuvirtide was one of the phenomenal successes in HIV-1 drug discovery research that has been made in recent years. There were many reports of modifying peptides from the N-terminal heptad repeat and CHR regions with the objective of improving their activity. A few laboratories also reported the identification of small-molecule inhibitors that apparently bind to the hydrophobic cavity identified in the gp41 core structure and prevent the CHR peptide binding to the N-terminal heptad repeat peptide, thereby prevent the formation of the typical six-helix bundle, which has been thought to be necessary for the fusion between HIV and cell membranes.
在过去十年中，大量活动致力于确定抑制HIV感染的新靶点，以及了解已确定的抗HIV-1药物的作用靶点。将源自HIV-1包膜糖蛋白gp41 C端七肽重复序列（CHR）区域的概念验证肽T-20（先前称为DP-178）转化为药物恩夫韦肽，是近年来HIV-1药物发现研究中取得的显著成功之一。有许多关于修饰N端七肽重复序列和CHR区域肽以提高其活性的报道。一些实验室还报告了鉴定出小分子抑制剂，这些抑制剂显然与gp41核心结构中确定的疏水腔结合，并阻止CHR肽与N端七肽重复序列肽结合，从而防止典型六螺旋束的形成，而六螺旋束被认为是HIV与细胞膜融合所必需的。
