title: Solution structure of RP 71955, a new 21 amino acid tricyclic peptide active against HIV-1 virus.
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.
authors.affiliation: Rhône-Poulenc Rorer S.A., Vitry-Sur-Seine, France.
authors.forename: D
authors.initials: D
authors.lastname: Fréchet
authors.forename: J D
authors.initials: JD
authors.lastname: Guitton
authors.forename: F
authors.initials: F
authors.lastname: Herman
authors.forename: D
authors.initials: D
authors.lastname: Faucher
authors.forename: G
authors.initials: G
authors.lastname: Helynck
authors.forename: B
authors.initials: B
authors.lastname: Monegier du Sorbier
authors.forename: J P
authors.initials: JP
authors.lastname: Ridoux
authors.forename: E
authors.initials: E
authors.lastname: James-Surcouf
authors.forename: M
authors.initials: M
authors.lastname: Vuilhorgne
mesh_terms: D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000737:chemistry* / Q000633:toxicity; D015700:HIV Envelope Protein gp41 / Q000737:chemistry; D015497:HIV-1 / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000633:toxicity; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D012996:Solutions; D013059:Spectrum Analysis, Raman
chemical_list: D000998:Antiviral Agents; D015700:HIV Envelope Protein gp41; D010456:Peptides, Cyclic; D012996:Solutions; C085040:RP 71955