2. Academic Validation
  3. Non-peptide entry inhibitors of HIV-1 that target the gp41 coiled coil pocket

Non-peptide entry inhibitors of HIV-1 that target the gp41 coiled coil pocket

  • Bioorg Med Chem Lett. 2010 Jan 15;20(2):612-7. doi: 10.1016/j.bmcl.2009.11.076.
Kent D Stewart 1,  Jeffrey R Huth,  Teresa I Ng,  Keith McDaniel,  Rebecca Newlin Hutchinson,  Vincent S Stoll,  Renaldo R Mendoza,  Edmund D Matayoshi,  Robert Carrick,  Hongmei Mo,  Jean Severin,  Karl Walter,  Paul L Richardson,  Leo W Barrett,  Robert Meadows,  Steve Anderson,  William Kohlbrenner,  Clarence Maring,  Dale J Kempf,  Akhter Molla,  Edward T Olejniczak
Affiliations

Affiliation

  • 1 Pharmaceutical Discovery Division, Abbott Laboratories, 100 Abbott Park Rd., R46Y, AP10, Abbott Park, IL 60064-6098, United States. kent.d.stewart@abbott.com
PMID: 20004576 DOI: 10.1016/j.bmcl.2009.11.076
Abstract

The ectodomain of HIV-1 gp41 mediates the fusion of viral and host cellular membranes. The peptide-based drug Enfuvirtide(1) is precedent that antagonists of this fusion activity may act as anti HIV-agents. Here, NMR screening was used to discover non-peptide leads against this target and resulted in the discovery of a new benzamide 1 series. This series is non-peptide, low molecular weight, and analogs have activity in a cell fusion assay with EC50 values ranging 3-41microM. Structural work on the gp41/benzamide 1 complex was determined by NMR spectroscopy using a designed model peptide system that mimics an open pocket of the fusogenic form of the protein.

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