Synthesis, biological evaluation, and docking studies of PAR2-AP-derived pseudopeptides as inhibitors of kallikrein 5 and 6
-
Beatrice Severino
, Ferdinando Fiorino
, Angela Corvino , Giuseppe Caliendo , Vincenzo Santagada , Diego Magno Assis , Juliana R. Oliveira , Luiz Juliano , Serena Manganelli , Emilio Benfenati , Francesco Frecentese , Elisa Perissutti und Maria Aparecida Juliano
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.
Acknowledgments
This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP – project-12/50191-4R), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq – projects 471340/2011-1 and 470388/2010-2).
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©2014 by De Gruyter
Artikel in diesem Heft
- Frontmatter
- Reviews
- Cholesterol lowering: role in cancer prevention and treatment
- The role of the Mpv17 protein mutations of which cause mitochondrial DNA depletion syndrome (MDDS): lessons from homologs in different species
- Research Articles/Short Communications
- Genes and Nucleic Acids
- Identification of a novel PHEX mutation in a Chinese family with X-linked hypophosphatemic rickets using exome sequencing
- Protein Structure and Function
- Complement activation by salivary agglutinin is secretor status dependent
- Synthesis, biological evaluation, and docking studies of PAR2-AP-derived pseudopeptides as inhibitors of kallikrein 5 and 6
- Membranes, Lipids, Glycobiology
- Recombinant HDL (Milano) protects endotoxin-challenged rats from multiple organ injury and dysfunction
- Cell Biology and Signaling
- miR-126 regulates platelet-derived growth factor receptor-α expression and migration of primary human osteoblasts
- Legumain expression, activity and secretion are increased during monocyte-to-macrophage differentiation and inhibited by atorvastatin
- Proteolysis
- Cell surface serine protease matriptase-2 suppresses fetuin-A/AHSG-mediated induction of hepcidin
Artikel in diesem Heft
- Frontmatter
- Reviews
- Cholesterol lowering: role in cancer prevention and treatment
- The role of the Mpv17 protein mutations of which cause mitochondrial DNA depletion syndrome (MDDS): lessons from homologs in different species
- Research Articles/Short Communications
- Genes and Nucleic Acids
- Identification of a novel PHEX mutation in a Chinese family with X-linked hypophosphatemic rickets using exome sequencing
- Protein Structure and Function
- Complement activation by salivary agglutinin is secretor status dependent
- Synthesis, biological evaluation, and docking studies of PAR2-AP-derived pseudopeptides as inhibitors of kallikrein 5 and 6
- Membranes, Lipids, Glycobiology
- Recombinant HDL (Milano) protects endotoxin-challenged rats from multiple organ injury and dysfunction
- Cell Biology and Signaling
- miR-126 regulates platelet-derived growth factor receptor-α expression and migration of primary human osteoblasts
- Legumain expression, activity and secretion are increased during monocyte-to-macrophage differentiation and inhibited by atorvastatin
- Proteolysis
- Cell surface serine protease matriptase-2 suppresses fetuin-A/AHSG-mediated induction of hepcidin