Synthesis, biological evaluation, and docking studies of PAR2-AP-derived pseudopeptides as inhibitors of kallikrein 5 and 6

Author(s):Show less -

Severino, Beatrice ^[1] ; Fiorino, Ferdinando ^[1] ; Corvino, Angela ^[1] ; Caliendo, Giuseppe ^[1] ; Santagada, Vincenzo ^[1] ; Assis, Diego Magno ^[2] ; Oliveira, Juliana R. ^[2] ; Juliano, Luiz ^[2] ; Manganelli, Serena ^[3] ; Benfenati, Emilio ^[3] ; Frecentese, Francesco ^[1] ; Perissutti, Elisa ^[1] ; Juliano, Maria Aparecida ^[2]

Affiliation

^[1] Univ Naples Federico II, Dipartimento Farm, I-80131 Naples - Italy

^[2] Univ Fed Sao Paulo, Escola Paulista Med, Dept Biofis, BR-04044020 Sao Paulo - Brazil

^[3] Ist Ric Farmacol Mario Negri, IRCCS, I-20156 Milan - Italy

• Document type: Journal article
• Source: Biological Chemistry; v. 396, n. 1, p. 45-52, JAN 2015.
• Web of Science Citations: 3

Abstract

A series of protease activated receptor 2 activating peptide (PAR2-AP) derivatives (1-15) were designed and synthesized. The obtained compounds were tested on a panel of human kallikreins (hKLK1, hKLK2, hKLK5, hKLK6, and hKLK7) and were found completely inactive toward hKLK1, hKLK2, and hKLK7. Aiming to investigate the mode of interaction between the most interesting compounds and the selected hKLKs, docking studies were performed. The described compounds distinguish the different human tissue kallikreins with compounds 1 and 5 as the best hKLK5 and hKLK6 inhibitors, respectively. (AU)

• FAPESP's process: 12/50191-4 - Synthesis, kinetic studies and applications of substrates and inhibitors for proteolytic enzymes
• Grantee: Maria Aparecida Juliano
• Support Opportunities: Research Projects - Thematic Grants