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The lack of selectivity of the large majority of such inhibitors, leading to the inhibition of MMPs in tissues other than the targeted one, has dramatically reduced the therapeutic interest in MMPIs. The recent development of efficient drug delivery systems that allow the transportation of a selected drug to its site of action has opened the way to new perspectives in the use of MMPIs. Here, a PAMAM\u2010based divalent dendron with two sulfonamidic residues was synthesized. This nanomolar inhibitor binds to the catalytic domain of two MMPs as well as to the transmembrane human carbonic anhydrases (hCAs) XII, which is present in the eye and considered an antiglaucoma target. In the animal model of an experimental dry eye, no occurrence of dotted staining in eyes treated with our inhibitor was observed, indicating no symptoms of corneal desiccation.<\/jats:p>","DOI":"10.1002\/chem.201504355","type":"journal-article","created":{"date-parts":[[2015,12,22]],"date-time":"2015-12-22T07:47:08Z","timestamp":1450770428000},"page":"1714-1721","source":"Crossref","is-referenced-by-count":20,"title":["A Divalent PAMAM\u2010Based Matrix Metalloproteinase\/Carbonic Anhydrase Inhibitor for the Treatment of Dry Eye Syndrome"],"prefix":"10.1002","volume":"22","author":[{"given":"B.","family":"Richichi","sequence":"first","affiliation":[{"name":"Department of Chemistry \u201cUgo Schiff\u201d University of Florence  via della Lastruccia 3\u201413 50019 Sesto Fiorentino Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Baldoneschi","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cUgo Schiff\u201d University of Florence  via della Lastruccia 3\u201413 50019 Sesto Fiorentino Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Burgalassi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Pisa  via Bonanno 33 56126 Pisa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Fragai","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cUgo Schiff\u201d University of Florence  via della Lastruccia 3\u201413 50019 Sesto Fiorentino Italy"},{"name":"CERM University of Florence  via Sacconi 6 50019 Sesto Fiorentino Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Vullo","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cUgo Schiff\u201d University of Florence  via della Lastruccia 3\u201413 50019 Sesto Fiorentino Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Akdemir","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Faculty of Pharmacy Bezmialem Vakif University  Vatan Caddesi 34093 Fatih, Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Dragoni","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cUgo Schiff\u201d University of Florence  via della Lastruccia 3\u201413 50019 Sesto Fiorentino Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Louka","sequence":"additional","affiliation":[{"name":"CERM University of Florence  via Sacconi 6 50019 Sesto Fiorentino Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Mamusa","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cUgo Schiff\u201d University of Florence  via della Lastruccia 3\u201413 50019 Sesto Fiorentino Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Monti","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Pisa  via Bonanno 33 56126 Pisa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Berti","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cUgo Schiff\u201d University of Florence  via della Lastruccia 3\u201413 50019 Sesto Fiorentino Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Novellino","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Napoli \u201cFederico II\u201d via Montesano 49  80131 Napoli Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. 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