4862F, a new inhibitor of HIV-1 protease, from the culture of Streptomyces I03A-04862

Molecules. 2012 Dec 27;18(1):236-43. doi: 10.3390/molecules18010236.

Abstract

We have isolated an extraordinary pentapeptide, called 4862F, from the culture broth of Streptomyces albosporus I03A-04862 by Diaion HP-20 macroporous adsorbent resin column, ODS-A and Sephadex LH-20 chromatography, followed by preparative HPLC. This peptide shows inhibitory activity against HIV-1 protease. The structure was elucidated by spectroscopic approaches, including ESI-MS and various NMR methods. Absolute configuration of the amino acid residues in 4862F was defined using Marfey's method, and the structure was identified as N,N,N-(trimethylated)-Tyr-L-Leu-L-Val-L-Leu-(dehydrated)-His. The peptide 4862F displays inhibitory activity against HIV-1 protease, with IC₅₀ values of 15.26 nM, using a fluorescence-based assay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / analysis
  • Chromatography, High Pressure Liquid
  • Fermentation
  • HIV Protease Inhibitors / chemistry*
  • HIV Protease Inhibitors / pharmacology*
  • Inhibitory Concentration 50
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Oligopeptides / chemistry*
  • Oligopeptides / pharmacology*
  • Peptides / chemistry*
  • Peptides / pharmacology*
  • Streptomyces / metabolism*

Substances

  • 4862F peptide
  • Amino Acids
  • HIV Protease Inhibitors
  • Oligopeptides
  • Peptides