title: Conformation-activity relationship of peptide T and new pseudocyclic hexapeptide analogs.
abstract: Peptide T (ASTTTNYT), a segment corresponding to residues 185-192 of gp120, the coat protein of HIV, has several important biological properties in vitro that have stimulated the search for simpler and possibly more active analogs. We have previously shown that pseudocyclic hexapeptide analogs containing the central residues of peptide T retain considerable chemotactic activity. We have now extended the design of this type of analogs to peptides containing different aromatic residues and/or Ser in lieu of Thr. The complex conformation-activity relationship of these analogs called for a reexamination of the basic conformational tendencies of peptide T itself. Here, we present an exhaustive NMR conformational study of peptide T in different media. Peptide T assumes a gamma-turn in aqueous mixtures of ethylene glycol, a type-IV beta-turn conformation in aqueous mixtures of DMF, and a type-II beta-turn conformation in aqueous mixtures of DMSO. The preferred conformations for the analogs were derived from modeling, starting from the preferred conformations of peptide T. The best models derived from the gamma-turn conformation of peptide T are those of peptides XII (DSNYSR), XIII (ETNYTK) and XVI (ESNYSR). The best models derived from the type-IV beta-turn conformation of peptide T are those of peptides XIV (KTTNYE) and XV (DSSNYR). No low-energy models could be derived starting from the type-II beta-turn conformation of peptide T. The analogs with the most favored conformations are also the most active in the chemotactic test.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Salerno, 84084-Fisciano Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: D'ursi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Caliendo
authors.forename: Elisa
authors.initials: E
authors.lastname: Perissutti
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Santagada
authors.forename: Beatrice
authors.initials: B
authors.lastname: Severino
authors.forename: Stefania
authors.initials: S
authors.lastname: Albrizio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bifulco
authors.forename: Susanna
authors.initials: S
authors.lastname: Spisani
authors.forename: Piero A
authors.initials: PA
authors.lastname: Temussi
mesh_terms: D000595:Amino Acid Sequence; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D009000:Monocytes / Q000187:drug effects; D019906:Nuclear Magnetic Resonance, Biomolecular; D015717:Peptide T / Q000737:chemistry* / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology*; D011487:Protein Conformation; D011789:Quantum Theory; D013329:Structure-Activity Relationship
chemical_list: D010456:Peptides, Cyclic; D015717:Peptide T