Solution Structure of RP 71955, a New 21 Amino Acid Tricyclic Peptide Active Against HIV-1 Virus

Biochemistry. 1994 Jan 11;33(1):42-50. doi: 10.1021/bi00167a006.

Abstract

The structure of RP 71955, a new tricyclic 21 amino acid peptide active against human immunodeficiency virus 1, was determined. Its amino acid composition was inferred from the results of fast atom bombardment mass spectrometry, nuclear magnetic resonance, Raman spectroscopy, and amino acid analysis. Its sequence could not be determined classically, using Edman degradation, given the lack of a free terminal NH2. It was deduced from the interpretation of interresidue nuclear Overhauser effects and confirmed by the sequencing of peptides obtained by limited chemical hydrolysis. It was found to be CLGIGSCNDFAGCGYAVVCFW. An internal amide bond between the NH2 of C1 and the gamma-COOH of D9 was observed, as well as two disulfide bridges, one between C1 and C13 and one between C7 and C19. The three-dimensional structure of RP 71955 was determined from nuclear magnetic resonance derived constraints using distance geometry, restrained molecular dynamics, nuclear Overhauser effect back calculation, and an iterative refinement using a full relaxation matrix approach. Analogies between the structure of RP 71955 and some functional domains of gp41, the transmembrane protein of human immunodeficiency virus 1, suggest hypotheses concerning the mode of action of RP 71955.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Antiviral Agents / chemistry*
  • Antiviral Agents / toxicity
  • HIV Envelope Protein gp41 / chemistry
  • HIV-1 / drug effects*
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Models, Molecular
  • Molecular Sequence Data
  • Peptides, Cyclic / chemistry*
  • Peptides, Cyclic / toxicity
  • Protein Conformation*
  • Sequence Homology, Amino Acid
  • Solutions
  • Spectrum Analysis, Raman

Substances

  • Antiviral Agents
  • HIV Envelope Protein gp41
  • Peptides, Cyclic
  • Solutions
  • RP 71955