Article ID Journal Published Year Pages File Type
2052968 FEBS Letters 2006 6 Pages PDF
Abstract

Fibroblast activation protein (FAP) is a serine protease of undefined endopeptidase specificity implicated in tumorigenesis. To characterize FAP’s P4–P2′ specificity, we synthesized intramolecularly quenched fluorescent substrate sets based on the FAP cleavage site in α2-antiplasmin (TSGP-NQ). FAP required substrates with Pro at P1 and Gly or d-amino acids at P2 and preferred small, uncharged amino acids at P3, but tolerated most amino acids at P4, P1′ and P2′. These substrate preferences allowed design of peptidyl-chloromethyl ketones that inhibited FAP, but not the related protease, dipeptidyl peptidase-4. Thus, FAP is a narrow specificity endopeptidase and this can be exploited for inhibitor design.

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