Glycosyltransferase inhibitors: a promising strategy to pave a path from laboratory to therapy

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Abnormal glycosylation is a common feature in disease that typically results from misregulation in expression and/or activity of glycosyltransferases (GTs) and glycosidases. Interfering with these enzymes, by developing a prospect of targeted inhibitors, has opened newer avenues to meet the challenge of abnormal glycosylation. Progress in GT inhibitors has been relatively slower in comparison to glycosidases. In case of GTs, their polyspecific nature, structural homology, overlapping specificities, multi-substrate catalytic mechanism and relatively less available 3D-structural data stance a big challenge to explore the whole potential of GT target inhibitors in comparison to glycosidases for therapeutic purposes. In this review, we focus on GT specific inhibitors, which are organised as conventional donor analogues (viz. donor, acceptor and transition state mimetic), glycomimetic, alternative inhibitor chemotype and metabolic chain terminator. Conventional donor analogues are however limited by the poor membrane permeability and chemical instability. Thus, in the last two decades, alternative inhibitor chemotypes caught attention as a promising lead, which are not structurally derived from GT substrates and possess drug like properties offering an alternate non-substrate like inhibitor based strategy for drug development. Although successful cellular GT-targeted molecules are yet to be achieved, recent designing of metabolic inhibitors i.e., dead end substrates are emerging as an impetus to explore the potential of GT families as therapeutic targets.
Original languageEnglish
Title of host publicationCarbohydrate Chemistry: Chemical and Biological Approaches
EditorsAmelia Pilar Rauter, Thisbe Lindhorst, Yves Queneau
PublisherRoyal Society Chemistry
Pages135-158
Volume43
ISBN (Electronic)978-1-78801-409-0
ISBN (Print)978-1-78801-003-0
DOIs
Publication statusPublished - 2018

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Glycosyltransferases
Glycoside Hydrolases
Therapeutics
Glycosylation
Substrate Specificity
Pharmaceutical Preparations
Permeability
Membranes
Enzymes

Cite this

Videira, P. A., Marcelo, F. M. B. M., & Grewal, R. K. (2018). Glycosyltransferase inhibitors: a promising strategy to pave a path from laboratory to therapy. In A. P. Rauter, T. Lindhorst, & Y. Queneau (Eds.), Carbohydrate Chemistry: Chemical and Biological Approaches (Vol. 43, pp. 135-158). Royal Society Chemistry. https://doi.org/10.1039/9781788010641-00135
Videira, P. A. ; Marcelo, Filipa Margarida Barradas Morais ; Grewal, Ravneet Kaur . / Glycosyltransferase inhibitors: a promising strategy to pave a path from laboratory to therapy. Carbohydrate Chemistry: Chemical and Biological Approaches. editor / Amelia Pilar Rauter ; Thisbe Lindhorst ; Yves Queneau. Vol. 43 Royal Society Chemistry, 2018. pp. 135-158
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Videira, PA, Marcelo, FMBM & Grewal, RK 2018, Glycosyltransferase inhibitors: a promising strategy to pave a path from laboratory to therapy. in AP Rauter, T Lindhorst & Y Queneau (eds), Carbohydrate Chemistry: Chemical and Biological Approaches. vol. 43, Royal Society Chemistry, pp. 135-158. https://doi.org/10.1039/9781788010641-00135

Glycosyltransferase inhibitors: a promising strategy to pave a path from laboratory to therapy. / Videira, P. A.; Marcelo, Filipa Margarida Barradas Morais; Grewal, Ravneet Kaur .

Carbohydrate Chemistry: Chemical and Biological Approaches. ed. / Amelia Pilar Rauter; Thisbe Lindhorst; Yves Queneau. Vol. 43 Royal Society Chemistry, 2018. p. 135-158.

Research output: Chapter in Book/Report/Conference proceedingChapter

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Videira PA, Marcelo FMBM, Grewal RK. Glycosyltransferase inhibitors: a promising strategy to pave a path from laboratory to therapy. In Rauter AP, Lindhorst T, Queneau Y, editors, Carbohydrate Chemistry: Chemical and Biological Approaches. Vol. 43. Royal Society Chemistry. 2018. p. 135-158 https://doi.org/10.1039/9781788010641-00135