Probing of CD4 binding pocket of HIV-1 gp120 glycoprotein using unnatural phenylalanine analogues

Xiaobo Yu, Poulami Talukder, Chandrabali Bhattacharya, Nour Eddine Fahmi, Jamie A. Lines, Larisa Dedkova, Joshua LaBaer, Sidney Hecht, Shengxi Chen

Research output: Contribution to journalArticle

6 Scopus citations


CD4-gp120 interaction is the first step for HIV-1 entry into host cells. A highly conserved pocket in gp120 protein is an attractive target for developing gp120 inhibitors or novel HIV detection tools. Here we incorporate seven phenylalanine derivatives having different sizes and steric conformations into position 43 of domain 1 of CD4 (mD1.2) to explore the architecture of the 'Phe43 cavity' of HIV-1 gp120. The results show that the conserved hydrophobic pocket in gp120 tolerates a hydrophobic side chain of residue 43 of CD protein, which is 12.2 Å in length and 8.0 Å in width. This result provides useful information for developing novel gp120 inhibitors or new HIV detection tools.

Original languageEnglish (US)
Pages (from-to)5699-5703
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Issue number24
StatePublished - Dec 15 2014



  • CD4
  • Keyword HIV-1 gp120
  • Microarray
  • Phe43 cavity
  • Phenylalanine derivatives

ASJC Scopus subject areas

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

Cite this