Covalent inhibitors of glycosidases and their applications in biochemistry and biology.

Department of Chemistry, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
Glycobiology (Impact Factor: 3.75). 09/2008; 18(8):570-86. DOI: 10.1093/glycob/cwn041
Source: PubMed

ABSTRACT Glycoside hydrolases are important enzymes in a number of essential biological processes. Irreversible inhibitors of this class of enzyme have attracted interest as probes of both structure and function. In this review we discuss some of the compounds used to covalently modify glycosidases, their use in residue identification, structural and mechanistic investigations, and finally their applications, both in vitro and in vivo, to complex biological systems.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Inhibitors synthesized by the Streptomyces lucensis VKPM AS-1743 and Streptomyces violaceus VKPM AS-1734 strains were studied for their influence on amylases of different origin. The effect of the inhibitors was shown to be different on fungal amylase, pancreatic amylase, and amylase from human blood. It has been found that the studied inhibitors are substances of a pseudooligosaccharide nature and exhibit their activity and stability over a wide range of pH and temperature values. The physico-chemical and biochemical properties of isolated inhibitors were compared with those of known microbial inhibitors of α-glucosidases.
    Applied Biochemistry and Microbiology 01/2015; 51(1). DOI:10.1134/S0003683815010159 · 0.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The development of selective anticancer vaccines that provide enhanced protection against tumor recurrence and metastasis has been the subject of intense research in the scientific community. The tumor-associated glycoprotein MUC1 represents a well-established target for cancer immunotherapy and has been used for the construction of various synthetic vaccine candidates. However, many of these vaccine prototypes suffer from an inherent low immunogenicity and are susceptible to rapid in vivo degradation. To overcome these drawbacks, novel fluorinated MUC1 glycopeptide-BSA/TTox conjugate vaccines have been prepared. Immunization of mice with the 4'F-TF-MUC1-TTox conjugate resulted in strong immune responses overriding the natural tolerance against MUC1 and producing selective IgG antibodies that are cross-reactive with native MUC1 epitopes on MCF-7 human cancer cells.
    Beilstein Journal of Organic Chemistry 01/2015; 11:155-61. DOI:10.3762/bjoc.11.15 · 2.80 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A series of N-bromoacetylglycosylamines and bromoketone C-glycosides were synthesised from complex xyloglucan oligosaccharide (XyGO) scaffolds as specific active-site affinity labels for endo-xyloglucanases. Compounds based on XXXG (Xyl3Glc4) and XLLG (Xyl3Glc4Gal2) oligosaccharides exhibited strikingly higher affinities and higher rates of irreversible inhibition than known cellobiosyl and new lactosyl disaccharide congeners when tested with endo-xyloglucanases from two distinct glycoside hydrolase (GH) families. Intact-protein mass spectrometry indicated that inactivation with XyGO derivatives generally resulted in a 1:1 labelling stoichiometry. Together, these results indicate that XyGO-based affinity reagents have significant potential as inhibitors and proteomic reagents for the identification and analysis of diverse xyloglucan-active enzymes in nature, to facilitate industrial enzyme applications.
    ChemBioChem 02/2015; 16(4). DOI:10.1002/cbic.201402663 · 3.06 Impact Factor

Full-text (2 Sources)

Available from
Nov 6, 2014