Structural Basis of the Thrombin Selectivity of a Ligand That Contains the Constrained Arginine Mimic (2S)-2-Amino-(3S)-3-(1-carbamimidoyl- piperidin-3-yl)-propanoic Acid at P1

• Published in: Journal of medicinal chemistry Vol. 43; no. 3; pp. 361 - 368
• Main Authors: Narasimhan, Lakshmi S, Rubin, J. Ronald, Holland, Debra R, Plummer, Janet S, Rapundalo, Stephen T, Edmunds, Jeremy E, St-Denis, Yves, Siddiqui, M. Arshad, Humblet, Christine
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 10.02.2000
• Subjects: Alanine - analogs & derivatives; Alanine - chemical synthesis; Alanine - chemistry; Amidines - chemical synthesis; Amidines - chemistry; Arginine - chemistry; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Crystallography, X-Ray; Factor Xa Inhibitors; Ligands; Medical sciences; Models, Molecular; Molecular Conformation; Molecular Mimicry; Pharmacology. Drug treatments; Structure-Activity Relationship; Thrombin - antagonists & inhibitors; Trypsin Inhibitors - chemical synthesis; Trypsin Inhibitors - chemistry; Angular nitrogen heterocycle; Thiazole derivatives; Non peptide compound; Thrombin; Anticoagulant; Selectivity; Modeling; Structure activity relation; Molecular model; Bicyclic compound; Chemical synthesis; Ungulata; Human; Molecular rigidity; Serine endopeptidases; Bovine; Enzyme; Peptidomimetic compound; Enzyme inhibitor; Inhibitor enzyme complex; Guanidines; In vitro; Peptidases; Vertebrata; Trypsin; Mammalia; Animal; Hydrolases; Carboxamide; Artiodactyla

We have studied the thrombin and trypsin complexed structures of a pair of peptidomimetic thrombin inhibitors, containing different P1 fragments. The first has arginine as its P1 fragment, and the second contains the constrained arginine mimic (2S)-2-amino-(3S)-3-(1-carbamimidoyl-piperidin-3-yl)-pro...