Synthesis and biological evaluation of novel biotin–iminoalditol conjugates

• Published in: Bioorganic & medicinal chemistry letters 2010-07, Vol.20 (14), p.4077-4079
• Main Authors: Pototschnig, Gerit, De Csáky, Christian Morales, Montenegro Burke, Jose R., Schitter, Georg, Stütz, Arnold E., Tarling, Chris A., Withers, Stephen G., Wrodnigg, Tanja M.
• Format: Article
• Language: English
• Subjects: Agrobacterium; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Biotin; Biotin - chemical synthesis; Biotin - pharmacology; Biotin–iminoalditol conjugate; Drug Evaluation, Preclinical; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Glycosidase inhibitor; Hydrolases; Iminoalditol; Medical sciences; Miscellaneous; Molecular Probes; Pharmacology. Drug treatments; Sugar Alcohols - chemical synthesis; Sugar Alcohols - pharmacology
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2010.05.084

The syntheses and biological evaluation of biotin–iminoalditol conjugates with d-gluco, l-ido, d-galacto configurations as well as of 2,5-dideoxy-2,5-imino-d-mannitol are reported. Biotin–iminosugar conjugates of different configuration such as d-gluco, d-galacto, l-ido as well as a furanoid representative in the d-manno configuration have been synthesised and exhibit powerful inhibition of β-glucosidase from Agrobacterium sp. with Ki values in the range of the respective parent compounds. Such molecular probes have potential for activity-based protein profiling taking advantage of the biotin–(strept)avidin interaction.