title: [Covalent chloramine inhibitors of blood platelet functions: computational indices for their reactivity and antiplatelet activity].
abstract: The quantum mechanics computation of the reactivities of chloramine derivatives of amino acids and taurine has been accomplished. A pair of computational indices that reflect a predisposition of alpha amino acid chloramines to chemical decay have been revealed. One of the indices was the dihedral angle for the chain of four atoms: carbons at beta- and alpha-positions, carbon of the carboxyl group, and carbonyl oxygen. The second index was the sum of partial charges for three or two carbon atoms in the chain. The amino acid chloramines with high values of the indices showed enhanced stability. Partial charges for active chlorine in known chloramines having different structures have been computed. The charges correlate with the rate constants of the reaction between chloramines and the thiol group of reduced glutathione. New derivatives of taurine chloramines have been constructed via the introduction of different substituents into the chloramine part. Among them, the amidoderivatives had the greatest charges of active chlorine (0.19-0.23). It was found in the study of the reactions of N-acetyl-N-chlorotaurine and N-propyonyl-N-chlorotaurine with amino acids and peptides possessing the thiol, thioester, or disulphide groups that the amidoderivatives manifested the thiol chemoselectivity. N-Acetyl-N-chlorotaurine and N-propionyl-N-chlorotaurine suppress the aggregation activity of blood platelets under their activation by the agonists ADP and collagen. It is not excluded that the amidoderivatives studied prevent platelet aggregation by a modification of the critical thiol group in the purine receptor P2Y12.
authors: D I
authors: DI
authors: Roshchupkin
authors: M A
authors: MA
authors: Murina
authors: V I
authors: VI
authors: Sergienko
mesh_terms: D002700:Chloramines / Q000737:chemistry; D004229:Dithiothreitol / Q000737:chemistry; D004355:Drug Stability; D006801:Humans; D008958:Models, Molecular; D010974:Platelet Aggregation / Q000187:drug effects*; D011485:Protein Binding; D011789:Quantum Theory; D058925:Receptors, Purinergic P2Y12 / Q000737:chemistry; D013329:Structure-Activity Relationship; D013654:Taurine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D002700:Chloramines; C548576:P2RY12 protein, human; D058925:Receptors, Purinergic P2Y12; D013654:Taurine; C043410:N-chlorotaurine; D004229:Dithiothreitol