D-Phe-Pro-Arg type thrombin inhibitors: unexpected selectivity by modification of the P1 moiety.
Synthesis of thrombin inhibitors and their binding mode to thrombin is described. Modification of the P1 moiety leads to an increased selectivity versus trypsin. The observed selectivity is discussed in view of their thrombin-inhibitor complex X-ray structures.
Lange
Udo E W
UE
BASF AG, D-67056, Ludwigshafen, Germany. wolfgang.hoeffken@basf-ag.de
Baucke
Dorit
D
Hornberger
Wilfried
W
Mack
Helmut
H
Seitz
Werner
W
Höffken
H Wolfgang
HW
D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014361:Trypsin Inhibitors / Q000737:chemistry / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009842:Oligopeptides; D014361:Trypsin Inhibitors; C077952:phenylalanyl-prolyl-arginine; D013917:Thrombin