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Synthesis of saccharin-glycoconjugates targeting carbonic anhydrase using a one-pot cyclization/deprotection strategy.
Murray, Akilah B; Quadri, Marta; Li, Haoxi; McKenna, Robert; Horenstein, Nicole A.
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  • Murray AB; Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, 32610, USA.
  • Quadri M; Department of Chemistry, College of Liberal Arts and Sciences, University of Florida, Gainesville, FL, 32611, USA.
  • Li H; Department of Chemistry, College of Liberal Arts and Sciences, University of Florida, Gainesville, FL, 32611, USA.
  • McKenna R; Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, 32610, USA.
  • Horenstein NA; Department of Chemistry, College of Liberal Arts and Sciences, University of Florida, Gainesville, FL, 32611, USA. Electronic address: horen@chem.ufl.edu.
Carbohydr Res ; 476: 65-70, 2019 Apr 01.
Article en En | MEDLINE | ID: mdl-30921738
Carbonic anhydrase IX (CA IX) has been identified as a biomarker and drug target for several malignant tumors due to its role in cancer cell growth and proliferation. Simple cyclic sulfonamides, like saccharin (SAC), have shown up to a 60-fold selectivity towards CA IX over other ubiquitous CA isoforms, with greater selectivity obtained applying the "tail-approach" to derivatize SAC with a methylene triazole linker that connected to a "tail" beta glucoside. These modifications of SAC led to an increased selectivity of more than 1000-fold towards CA IX, whereas clinically available CA inhibitors show little to no isoform selectivity. As part of our interest in the development of new CA inhibitors, we found the existing synthetic protocol, which relies on a N-tert-butyl saccharin intermediate, to be problematic in the final deprotection steps. We therefore describe an alternative approach to the synthesis of these compounds featuring a gentle "one pot" deprotection/cyclization as the final synthetic step, and report new galactosyl and glucosyl conjugates with low to mid nM inhibition of CA IX.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sacarina / Glicoconjugados / Inhibidores Enzimáticos / Anhidrasa Carbónica IX Tipo de estudio: Guideline Idioma: En Revista: Carbohydr Res Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sacarina / Glicoconjugados / Inhibidores Enzimáticos / Anhidrasa Carbónica IX Tipo de estudio: Guideline Idioma: En Revista: Carbohydr Res Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos