title: Selectivity enhancement induced by substitution of non-natural analogues of arginine and lysine in arginine-based thrombin inhibitors.
abstract: Seven non-natural analogues of arginine and lysine have been substituted in an established arginine-based thrombin inhibitor. Four of the new compounds exhibited significant thrombin inhibition (K(i)'s 0.53-3.95 microM) and were subsequently tested for selectivity against trypsin. The two best compounds gave selectivity ratios of 962 and 525 (trypsin/thrombin), improving upon the parent compound.
authors.affiliation: Department of Pharmaceutical Sciences, Medical University of South Carolina, PO Box 250140, 29425, Charleston, SC, USA.
authors.forename: K P
authors.initials: KP
authors.lastname: Kokko
authors.forename: C E
authors.initials: CE
authors.lastname: Arrigoni
authors.forename: T A
authors.initials: TA
authors.lastname: Dix
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites / Q000502:physiology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D013917:Thrombin / Q000037:antagonists & inhibitors*; D014357:Trypsin / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D001120:Arginine; D014357:Trypsin; D013917:Thrombin; D008239:Lysine