title: A conformational study of Lys-Arg-Asp-Ser and analogs, a series of potent antithrombotic peptides. An approach based on simulated annealing and 1H NMR.
abstract: Simulated annealing techniques were used to explore the conformational space of the potent antithrombotic peptide L.Lys-L.Arg-L.Asp-L.Ser (KRDS) and of two analogs: D.Lys-L.Arg-L.Asp-L.Ser (KDRDS), which is inactive, and L.Lys-L.Arg-L.Glu-L.Glu (KREE), which exhibits a strong biological activity. For each peptide, a set of initial conformations was generated and submitted to simulated annealing, including a heating to 1000 K followed by a cooling to 300 K. 200 resulting conformations of each compound were analyzed and classified according to the network of electrostatic interactions involving charged side chains and charged C- and N-terminal groups. A reduced number of conformational classes was obtained and conformations corresponding to predominant classes were found to be in qualitative agreement with structural parameters deduced from 1H NMR spectra. A comparison between the classes of the active and non active peptide was achieved. Some conformations were found to be specific of active peptides.
authors.affiliation: Institut Curie, Université Paris VI, France.
authors.forename: S
authors.initials: S
authors.lastname: Meddeb
authors.forename: J P
authors.initials: JP
authors.lastname: Demaret
authors.forename: J P
authors.initials: JP
authors.lastname: Ballini
authors.forename: A M
authors.initials: AM
authors.lastname: Fiat
authors.forename: P
authors.initials: P
authors.lastname: Jollès
authors.forename: M
authors.initials: M
authors.lastname: Ptak
authors.forename: P
authors.initials: P
authors.lastname: Vigny
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D005343:Fibrinolytic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D007781:Lactoferrin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011487:Protein Conformation; D013696:Temperature
chemical_list: D005343:Fibrinolytic Agents; D009842:Oligopeptides; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; C090249:lysyl-arginyl-glutamyl-glutamic acid; C056549:KRDS peptide; D007781:Lactoferrin