Discovery of HIV fusion inhibitors targeting gp41 using a comprehensive α-helix mimetic library

The evaluation of a comprehensive alpha-helix mimetic library for binding the gp41 NHR hydrophobic pocket recognizing an intramolecular CHR alpha-helix provided a detailed depiction of structural features required for binding and led to the discovery of small molecule inhibitors (K-i 0.6-1.3 mu M) that not only match or exceed the potency of those disclosed over the past decade, but that also exhibit effective activity in a cell-cell fusion assay (IC50 5-8 mu M). (C) 2012 Elsevier Ltd. All rights reserved.