10.6084/m9.figshare.3896154.v1 Marta Abellán-Flos Marta Abellán-Flos Muhammet Tanç Muhammet Tanç Claudiu T. Supuran Claudiu T. Supuran Stéphane P. Vincent Stéphane P. Vincent Multimeric xanthates as carbonic anhydrase inhibitors Taylor & Francis Group 2016 multimeric presentation molecules 18 monomeric species selectivity xanthate moieties ligand affinity CA isoforms Multimeric xanthates carbonic anhydrase inhibitors multimeric xanthates xanthate units inhibition Carbonic anhydrases carbohydrate-processing enzymes monovalent analogues study reports glycosidase enzyme 2016-09-28 15:14:13 Journal contribution https://tandf.figshare.com/articles/journal_contribution/Multimeric_xanthates_as_carbonic_anhydrase_inhibitors/3896154 <p>The field of multivalent inhibition of enzymes is growing exponentially from the first reported multivalent effect on a glycosidase enzyme. However, the investigations have generally remained restricted to carbohydrate-processing enzymes. Carbonic anhydrases are ubiquitous metallo-enzymes involved in many key biological processes, that catalyze the reversible hydration/dehydration of . This study reports the first synthesis of multimeric xanthates addressing the selectivity and potency of CA multivalent inhibition. Six multivalent compounds containing three, four, and six xanthate moieties were prepared and assayed against four relevant CA isoforms together with their monovalent analogues. Some of the multimers were stronger inhibitors than the monomeric species. For hCA I, the two best molecules <b>18</b> and <b>20</b> showed an improvement of the ligand affinity of 4.8 and 2.3 per xanthate units (valence-corrected values), respectively, which corresponds to a clear multivalent effect. Moreover, the biochemical assays demonstrated that the multimeric presentation of xanthates, also affected the selectivity of the relative inhibition among the four CAs assayed.</p>