Amino Acid derivatives as new zinc binding groups for the design of selective matrix metalloproteinase inhibitors.

Abstract

A number of matrix metalloproteinases (MMPs) are important medicinal targets for conditions ranging from rheumatoid arthritis to cardiomyopathy, periodontal disease, liver cirrhosis, multiple sclerosis, and cancer invasion and metastasis, where they showed to have a dual role, inhibiting or promoting important processes involved in the pathology. MMPs contain a zinc (II) ion in the protein active site. Small-molecule inhibitors of these metalloproteins are designed to bind directly to the active site metal ions. In an effort to devise new approaches to selective inhibitors, in this paper, we describe the synthesis and preliminary biological evaluation of amino acid derivatives as new zinc binding groups (ZBGs). The incorporation of selected metal-binding functions in more complex biphenyl sulfonamide moieties allowed the identification of one compound able to interact selectively with different MMP enzymatic isoforms.

• Authors: Mariateresa Giustiniano, Paolo Tortorella, Mariangela Agamennone, Antonella Di Pizio, Armando Rossello, Elisa Nuti, Isabel Gomez-Monterrey, Ettore Novellino, Pietro Campiglia, Ermelinda Vernieri, Marina Sala, Alessia Bertamino, Alfonso Carotenuto
• Journal: Journal of amino acids (J Amino Acids) Vol. 2013 Pg. 178381 ( 2013) ISSN: 2090-0104 [Print] Egypt
• PMID: 23555050 (Publication Type: Journal Article)