Imagine being able to stop the human immunodeficiency virus (HIV) before it even enters the cell. A wide range of compounds, generally known as entry inhibitors, have recently been designed to do just this.

Irwin Chaiken’s research group at Drexel University College of Medicine, Philadelphia, USA, in collaboration with researchers at Johns Hopkins University and Bryn Mawr College, USA, studied peptide-based leads that can simultaneously block the virus’ gp120 glycoprotein from undergoing two key interactions, with target cell CD4 and a co-receptor, required for virus entry into the cell.

Chaiken and colleagues set out to minimize the structural complexity of a lead series of peptide triazole HIV-1 gp120 inhibitors. Through a combination of chemical synthesis, molecular binding analysis, and antiviral cell infection assays, they identified entry inhibitor leads that can be used to develop therapeutic and microbicidal agents to treat or prevent HIV-1 infections. Their results help define the minimal pharmacophore that enables dual antagonism of gp120; they also help pave the way for the future design of advanced peptidomimetic HIV-1 inhibitor leads.

• The Active Core in a Triazole Peptide Dual-Site Antagonist of HIV-1 gp120
  M. Umashankara, K. McFadden, I. Zentner, A. Schön, S. Rajagopal et al.,
  ChemMedChem 2010, 5(11).
  DOI: 10.1002/cmdc.201000222