Anti-HIV-1 activity of chemically modified heparins: correlation between binding to the V3 loop of gp120 and inhibition of cellular HIV-1 infection in vitro

Biochemistry. 1994 Jun 7;33(22):6974-80. doi: 10.1021/bi00188a029.

Abstract

Chemically modified heparins were tested for their activities in (i) inhibiting HIV-1 replication in vitro and (ii) inhibiting the binding to recombinant HIV-1 gp120 of monoclonal antibodies specific for the V3 loop. The results reveal that N-desulfation reduces activity, although this is largely restored on N-acetylation. Selective O-desulfation also markedly reduces activity, whereas carboxyl reduction has little effect. Overall these results show that the anti-HIV-1 activity of heparin does not depend simply on negative density, and indicate instead that particular structures, notably O-sulfates, are involved. Our studies reveal that for chemically modified heparins and heparin-derived fragments there is a striking correlation between anti-HIV-1 activity in vitro and binding to the V3 loop of gp120 in solid phase ELISA. This strongly suggests that the heparin exerts its anti-HIV-1 activity by binding to the V3 loop of gp120.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Amino Acid Sequence
  • Animals
  • Antiviral Agents / metabolism
  • Antiviral Agents / pharmacology*
  • CD4-Positive T-Lymphocytes / microbiology
  • Cattle
  • Enzyme-Linked Immunosorbent Assay
  • HIV Envelope Protein gp120 / metabolism*
  • HIV-1 / drug effects*
  • Heparin / analogs & derivatives*
  • Heparin / metabolism
  • Heparin / pharmacology
  • Humans
  • Magnetic Resonance Spectroscopy
  • Molecular Sequence Data
  • Peptide Fragments / metabolism*
  • Protein Binding
  • Structure-Activity Relationship
  • Sulfates
  • Swine

Substances

  • Antiviral Agents
  • HIV Envelope Protein gp120
  • HIV envelope protein gp120 (305-321)
  • Peptide Fragments
  • Sulfates
  • Heparin