Inhibition of human matriptase by eglin c variants.
Based on the enzyme specificity of matriptase, a type II transmembrane serine protease (TTSP) overexpressed in epithelial tumors, we screened a cDNA library expressing variants of the protease inhibitor eglin c in order to identify potent matriptase inhibitors. The most potent of these, R(1)K(4)'-eglin, which had the wild-type Pro(45) (P1 position) and Tyr(49) (P4' position) residues replaced with Arg and Lys, respectively, led to the production of a selective, high affinity (K(i) of 4nM) and proteolytically stable inhibitor of matriptase. Screening for eglin c variants could yield specific, potent and stable inhibitors to matriptase and to other members of the TTSP family.
Department of Pharmacology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Que., Canada J1H 5N4.
Antoine
A
Désilets
Jean-Michel
JM
Longpré
Marie-Eve
ME
Beaulieu
Richard
R
Leduc
D019943:Amino Acid Substitution; D004789:Enzyme Activation; D015723:Gene Library; D006801:Humans; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000235:genetics; D013379:Substrate Specificity
D011506:Proteins; C028656:eglin proteinase inhibitors; D012697:Serine Endopeptidases; C485596:ST14 protein, human