354580-62-4Relevant academic research and scientific papers
Identification of gp120 Residue His105 as a Novel Target for HIV-1 Neutralization by Small-Molecule CD4-Mimics
Abrams, Cameron F.,Anang, Saumya,Chen, Junhua,Fritschi, Christopher J.,Hendrickson, Wayne A.,Liang, Shuaiyi,Madani, Navid,Mohammadi, Mohammadjavad,Moraca, Francesca,Smith, Amos B.,Sodroski, Joseph G.
supporting information, p. 1824 - 1831 (2021/11/16)
The design and synthesis of butyl chain derivatives at the indane ring 3-position of our lead CD4-mimetic compound BNM-III-170 that inhibits human immunodeficiency virus (HIV-1) infection are reported. Optimization efforts were guided by crystallographic and computational analysis of the small-molecule ligands of the Phe43 cavity of the envelope glycoprotein gp120. Biological evaluation of 11-21 revealed that members of this series of CD4-mimetic compounds are able to inhibit HIV-1 viral entry into target cells more potently and with greater breadth compared to BNM-III-170. Crystallographic analysis of the binding pocket of 14, 16, and 17 revealed a novel hydrogen bonding interaction between His105 and a primary hydroxyl group on the butyl side chain. Further optimization of this interaction with the His105 residue holds the promise of more potent CD4-mimetic compounds.
