Blocking HIV-1 entry by a gp120 surface binding inhibitor

Lun K. Tsou, Chin Ho Chen, Ginger E. Dutschman, Yung Chi Cheng, Andrew D. Hamilton

Research output: Contribution to journalArticlepeer-review


We report the mode of action of a proteomimetic compound that binds to the exterior surface of gp120 and blocks HIV-1 entry into cells. Using a one cycle time-of-addition study and antibody competition binding studies, we have determined that the compound blocks HIV-1 entry through modulation of key protein-protein interactions mediated by gp120. The compound exhibits anti-HIV-1 replication activities against several pseudotype viruses derived from primary isolates and the resistant strains isolated from existing drug candidates with equal potency. Together, these data provide evidence that the proteomimetic compound represents a novel class of HIV-1 viral entry inhibitor that functions through protein surface recognition in analogy to an antibody.

Original languageEnglish (US)
Pages (from-to)3358-3361
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Issue number9
StatePublished - May 1 2012


  • Calix[4]arene scaffold
  • HIV-entry inhibitor
  • Protein surface recognition
  • Proteomimetic inhibitor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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