Anti-HIV-1 Small Molecule-Peptide Conjugates for Studying Target Binding of Small Molecule Fusion Inhibitors

摘要

The HIV-1 fusion protein gp41 plays a critical role mediating the fusion of viral and cellular membranes, which makes it an ideal drug target for the 'design of HIV fusion inhibitors. There are two functional domains, designated NHR and CHR in the gp41 ectodomain, which can interact with each other to form a fusogenic 6-helical bundle (6-HB), thus making the two envelopes join and fuse. The formation of the 6-HB is the final key step in the entry of HIV-1 to the CD4 T cell.Any compounds that prevent 6-HB formation can interrupt the membrane fusion process, thus inhibiting the entry of HIV-1 to the target cell and stopping the infection of HIV-1 at an early stage. Peptides derived from CHR, e.g., T20 and SFT, are highly potent HIV fusion inhibitors because they bind to the corresponding NHR to competitively inhibit the native interaction of two functional regions.