Comparison of hirudin and hirudin PA C-terminal fragments and related analogs as antithrombin agents.
Hirudin PA54-66 and related hirudin fragment analogs were synthesized and assessed for their inhibition of thrombin-induced fibrin-clot formation in plasma. Pro58 and Ala63-Tyr64 modifications in the hirudin sequence resulted in increased antithrombin potency, whereas Asp62, Ala63 and Tyr64 individual substitutions each resulted in a loss of potency.
Krstenansky
J L
JL
Merrell Dow Research Institute, Cincinnati, Ohio 45215.
Owen
T J
TJ
Yates
M T
MT
Mao
S J
SJ
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D000991:Antithrombins / Q000302:isolation & purification / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D006629:Hirudins / Q000302:isolation & purification / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000302:isolation & purification / Q000494:pharmacology*; D011487:Protein Conformation; D013917:Thrombin
D000596:Amino Acids; D000991:Antithrombins; D006629:Hirudins; D010446:Peptide Fragments; D013917:Thrombin