Aspartame and aspartame derivatives effect human thrombin catalytic activity.
The study of small Asp-Phe analogs was undertaken since this dipeptide sequence is critical in fibrinogen recognition and catalysis. The inhibition of clotting activity by Asp-Phe-methyl ester (aspartame), formyl-Asp-Phe-methyl ester and acetyl-Asp-Phe was biphasic in all cases, indicating the presence of at least two binding sites. The N-terminally blocked derivatives are stronger inhibitors than aspartame. In contrast, tosyl-Gly-Pro-Arg-p'-nitroanilide hydrolysis was inhibited minimally by Asp-Phe-methyl, ester [Ki(app)=98 mM]. Acetyl-Asp-Phe inhibition of thrombin amidase activity was biphasic, tenfold stronger and appeared to be strongly cooperative. These results are discussed with respect to the inhibition of alpha-thrombin by ATP.
Scheffler
Julie E
JE
Department of Chemistry and Biochemistry, University of Denver, 2190 E. Iliff Avenue, Olin Hall 202, Denver, CO 80208-2436, USA.
Berliner
Lawrence J
LJ
D000581:Amidohydrolases / Q000037:antagonists & inhibitors; D000595:Amino Acid Sequence; D001218:Aspartame / Q000494:pharmacology*; D001665:Binding Sites; D001777:Blood Coagulation / Q000187:drug effects; D002384:Catalysis; D004151:Dipeptides / Q000494:pharmacology; D006801:Humans; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004151:Dipeptides; D013917:Thrombin; D000581:Amidohydrolases; C019665:amidase; D001218:Aspartame