A CONFORMATIONAL STUDY OF LYS-ARG-ASP-SER AND ANALOGS, A SERIES OF POTENT ANTITHROMBOTIC PEPTIDES - AN APPROACH BASED ON SIMULATED ANNEALING AND H-1-NMR

Simulated annealing techniques were used to explore the conformational space of the potent antithrombotic peptide L.Lys-L.Arg-L.Asp-L.Ser (K RDS) and of two analogs: D.Lys-L.Arg-L.Asp-L.Ser (K(D)RDS), which is i nactive, and L.Lys-L.Arg-L.Glu-L.Glu (KREE), which exhibits a strong b iological activity. For each peptide, a set of initial conformations w as 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 networ k of electrostatic interactions involving charged side chains and char ged C- and N- terminal, groups. A reduced number of conformational cla sses was obtained and conformations corresponding to predominant class es were found to be in qualitative agreement with structural parameter s deduced from H-1 NMR spectra. A comparison between the classes of th e active and non active peptide was achieved. Some conformations were found to be specific of active peptides.