ABSTRACT
The literature data on effective approaches to the development of the novel peptidomimetics, antagonists of fibrinogen GP IIb/IIIa receptors as potential antithrombotic agents are generalized and systematized in the review. The data obtained by the authors on the synthesis and properties of novel peptidomimetics are reported.
Subject(s)
Oligopeptides/chemical synthesis , Platelet Aggregation Inhibitors/chemical synthesis , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Humans , Oligopeptides/pharmacology , Platelet Aggregation Inhibitors/chemistry , Platelet Aggregation Inhibitors/pharmacology , Protein Conformation , Structure-Activity RelationshipABSTRACT
On the basis of the two-dimensional 1H NMR studies the conformation of melanocyte inhibiting hormone (HCl.Pro-Leu-Gly-NH2, MIF) and its five analogues with p-substituted phenylalanine has been determined. Structure-antidepressant activity relationship (examined by the Porsolt test) of MIF and its analogues has been estimated by means of the multivariate statistical analysis, the vicinal spin coupling constants, which determine phi and chi dihedral angles of the second amino acid and phi and dihedral angle of glycine, being selected as structural parameters. It is shown that a biologically active conformation (10-membered beta-turn II) is realized for the considered peptides.
