Ramsdale T E, Andrews P R, Nice E C
Centre for Drug Design and Development, University of Queensland, St. Lucia, Australia.
FEBS Lett. 1993 Nov 1;333(3):217-22. doi: 10.1016/0014-5793(93)80657-g.
Peptide T is currently in phase II clinical trials for the treatment of AIDS-associated dementia. Its putative mode of action is inhibition of binding of the HIV envelope protein (gp120) to its cellular receptor (CD4), thus preventing viral infectivity and gp120-induced neuronal toxicity. However, a number of reports have appeared in the literature which have failed to observe any inhibitory activity of Peptide T on CD4-gp120 binding, thus casting doubt on this hypothesis. This study uses a novel biosensor technique to demonstrate that Peptide T does bind to CD4 and that this binding can be specifically inhibited by an anti-CD4 monoclonal antibody. A detailed analysis of the kinetics of the interaction is presented.
肽T目前正处于治疗艾滋病相关痴呆症的二期临床试验阶段。其假定的作用方式是抑制HIV包膜蛋白(gp120)与其细胞受体(CD4)的结合,从而防止病毒感染性以及gp120诱导的神经元毒性。然而,文献中出现了一些报告,未能观察到肽T对CD4-gp120结合有任何抑制活性,因此对这一假设产生了怀疑。本研究使用一种新型生物传感器技术来证明肽T确实能与CD4结合,并且这种结合可被抗CD4单克隆抗体特异性抑制。本文还对相互作用的动力学进行了详细分析。