title: Synthesis and binding monitoring of a new nanomolar PAMAM-based matrix metalloproteinases inhibitor (MMPIs).
abstract: Dendrimers are efficient drug delivery systems particularly useful in ocular diseases. In particular, low generation PAMAM dendrimers are non-toxic and non-immunogenic and they provide an enhancement of the residence time of drugs in the eyes. In this context, the synthesis of the PAMAM-based matrix metalloproteinases inhibitor 5, is reported. In particular, we demonstrated that 5 strongly binds (18.0nM±2.5nM) MMP-9, the most relevant MMP responsible of ocular surface damages in induced dry eyes syndrome (DES).
authors.affiliation: Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino (FI), Italy; CERM, University of Florence, Via Sacconi 6, 50019 Sesto Fiorentino (FI), Italy.
authors.forename: Linda
authors.initials: L
authors.lastname: Cerofolini
authors.affiliation: Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino (FI), Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Baldoneschi
authors.affiliation: Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino (FI), Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Dragoni
authors.affiliation: Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino (FI), Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Storai
authors.affiliation: Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino (FI), Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Mamusa
authors.affiliation: Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino (FI), Italy.
authors.forename: Debora
authors.initials: D
authors.lastname: Berti
authors.affiliation: Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino (FI), Italy; CERM, University of Florence, Via Sacconi 6, 50019 Sesto Fiorentino (FI), Italy. Electronic address: fragai@cerm.unifi.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Fragai
authors.affiliation: Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino (FI), Italy. Electronic address: barbara.richichi@unifi.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Richichi
authors.affiliation: Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino (FI), Italy; CERM, University of Florence, Via Sacconi 6, 50019 Sesto Fiorentino (FI), Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Nativi
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005470:Fluorometry; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000302:isolation & purification / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D050091:Dendrimers; D061965:Matrix Metalloproteinase Inhibitors; C104700:PAMAM Starburst; D020780:Matrix Metalloproteinase 9
keywords: Dendrimers; Inhibitors; Metalloproteins; NMR spectroscopy; Sulphonamidic scaffold