Tryptophan dendrimers that inhibit HIV replication, prevent virus entry and bind to the HIV envelope glycoproteins gp120 and gp41

Eur J Med Chem. 2015 Dec 1:106:34-43. doi: 10.1016/j.ejmech.2015.10.031. Epub 2015 Oct 21.

Abstract

Dendrimers containing from 9 to 18 tryptophan residues at the peryphery have been efficiently synthesized and tested against HIV replication. These compounds inhibit an early step of the replicative cycle of HIV, presumably virus entry into its target cell. Our data suggest that HIV inhibition can be achieved by the preferred interaction of the compounds herein described with glycoproteins gp120 and gp41 of the HIV envelope preventing interaction between HIV and the (co)receptors present on the host cells. The results obtained so far indicate that 9 tryptophan residues on the periphery are sufficient for efficient gp120/gp41 binding and anti-HIV activity.

Keywords: AIDS; Antiviral agents; HIV; Tryptophan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Binding Sites
  • Dendrimers / chemical synthesis
  • Dendrimers / chemistry
  • Dendrimers / pharmacology*
  • Dose-Response Relationship, Drug
  • HIV / drug effects*
  • HIV / metabolism
  • HIV Envelope Protein gp120 / metabolism*
  • HIV Envelope Protein gp41 / metabolism*
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Protein Binding / drug effects
  • Receptors, HIV / metabolism
  • Structure-Activity Relationship
  • Tryptophan / chemical synthesis
  • Tryptophan / chemistry
  • Tryptophan / pharmacology*
  • Tumor Cells, Cultured
  • Virus Internalization / drug effects*
  • Virus Replication / drug effects*

Substances

  • Anti-HIV Agents
  • Dendrimers
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp41
  • Receptors, HIV
  • Tryptophan