title: 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.affiliation: Dipartimento di Chimica Farmaceutica e Tossicologica, Università di Napoli "Federico II," Via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Giustiniano
authors.forename: Paolo
authors.initials: P
authors.lastname: Tortorella
authors.forename: Mariangela
authors.initials: M
authors.lastname: Agamennone
authors.forename: Antonella
authors.initials: A
authors.lastname: Di Pizio
authors.forename: Armando
authors.initials: A
authors.lastname: Rossello
authors.forename: Elisa
authors.initials: E
authors.lastname: Nuti
authors.forename: Isabel
authors.initials: I
authors.lastname: Gomez-Monterrey
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Pietro
authors.initials: P
authors.lastname: Campiglia
authors.forename: Ermelinda
authors.initials: E
authors.lastname: Vernieri
authors.forename: Marina
authors.initials: M
authors.lastname: Sala
authors.forename: Alessia
authors.initials: A
authors.lastname: Bertamino
authors.forename: Alfonso
authors.initials: A
authors.lastname: Carotenuto
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