Abellán-Flos, Marta Tanç, Muhammet Supuran, Claudiu T. Vincent, Stéphane P. Multimeric xanthates as carbonic anhydrase inhibitors <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> 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
    https://tandf.figshare.com/articles/journal_contribution/Multimeric_xanthates_as_carbonic_anhydrase_inhibitors/3896154
10.6084/m9.figshare.3896154.v1