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>