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.
Désilets
Antoine
A
Department of Pharmacology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Que., Canada J1H 5N4.
Longpré
Jean-Michel
JM
Beaulieu
Marie-Eve
ME
Leduc
Richard
R
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