Details

Autor(en) / Beteiligte

• Edosada, Conrad Yap
• Quan, Clifford
• Tran, Thuy
• Pham, Victoria
• Wiesmann, Christian
• Fairbrother, Wayne
• Wolf, Beni B.

Titel

Peptide substrate profiling defines fibroblast activation protein as an endopeptidase of strict Gly2‐Pro1‐cleaving specificity

Ist Teil von

• FEBS letters, 2006-03, Vol.580 (6), p.1581-1586

Erscheinungsjahr

2006

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• Fibroblast activation protein (FAP) is a serine protease of undefined endopeptidase specificity implicated in tumorigenesis. To characterize FAP's P 4 – P 2 ′ 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, P 1 ′ and P 2 ′ . 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.