Abstract：
Identification and assessment of novel targets is essential to combat drug resistance in the treatment of HIV/AIDS. HIV Capsid (HIV-CA), the protein playing a major role in both the early and late stages of the viral life cycle, has emerged as an important target. We have applied an NMR fragment screening platform and identified molecules that bind to the N-terminal domain (NTD) of HIV-CA at a site close to the interface with the C-terminal domain (CTD). Using X-ray crystallography, we have been able to obtain crystal structures to identify the binding mode of these compounds. This allowed for rapid progression of the initial, weak binding, fragment starting points to compounds 37 and 38, which have 19F-pKi values of 5.3 and 5.4 respectively.
摘要：
识别和评估新的靶标对于对抗HIV/AIDS治疗中的耐药性至关重要。HIV衣壳(HIV-CA),蛋白质在病毒生命周期的早期和晚期都起着重要作用，已经成为一个重要的目标。我们已经应用了NMR片段筛选平台，并鉴定了在靠近C端结构域（CTD）界面的位点与HIV-CA的N端结构域（NTD）结合的分子。用X射线晶体学,我们已经能够获得晶体结构，以确定这些化合物的结合模式。这使得最初的进展迅速，弱结合，片段起始指向化合物37和38,其19F-pKi值分别为5.3和5.4。
