Influence of chain shortening on the inhibitor properties of hirudin and eglin c.
To find out minimal sizes of the proteinase inhibitor proteins hirudin and eglin necessary for their biological activity the inhibitors were incubated with exopeptidases. From the incubation mixtures shortened derivatives were isolated and characterized. Eglin c can be N-terminally shortened by up to 6 amino-acid residues without any loss of affinity towards chymotrypsin. The complex of thrombin with hirudin lacking 3 C-terminal amino-acid residues showed a 15-20-fold increased Ki value as found previously for desulfato-hirudin and desulfato-hirudin shortened by 2 amino-acid residues. Obviously, the C-terminal part of the hirudin molecule has a positive influence on its affinity to thrombin.
Dodt
J
J
Klinische Chemie und Klinische Biochemie, Universität München.
Seemüller
U
U
Fritz
H
H
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D020789:Cathepsin C; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D006629:Hirudins / Q000494:pharmacology*; D006868:Hydrolysis; D010455:Peptides / Q000032:analysis; D011480:Protease Inhibitors; D011506:Proteins / Q000494:pharmacology*; D015843:Serpins; D013329:Structure-Activity Relationship
D000596:Amino Acids; D006629:Hirudins; D010455:Peptides; D011480:Protease Inhibitors; D011506:Proteins; D015843:Serpins; C028656:eglin proteinase inhibitors; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D020789:Cathepsin C