Abstract
An increasing appreciation of carbohydrates as components of natural products has uncovered new opportunities in carbohydrate-based drug design. Glycosylated natural products produced by microorganisms contain a variety of different sugars. Usually the biosynthetic pathways to deoxysugars start from a monosacchride-1-phosphate which is converted to a NDP-hexose by a nucleotidyltransferase. Modification of this intermediate by different enzymes (e.g. dehydratases, epimerases, aminotransferases) yields the final sugar. In contrast to microorganisms, plant products mostly contain glucose, galactose, rhamnose and xylose as structural elements. In all organisms the nucleotide-activated sugar is attached to an aglycon by a glycosyltransferrase (GT). As no single universal GT has been uncovered yet, accomplishing the generation of novel glycosylated compounds requires a deep understanding of the function of glycosyltransferases (GTs) and its specificity. In this review we will present important drugs that contain sugar components. We will give an overview about the existing natural product GTs and we will discuss the structural features of GTs. Through specific examples within different compound classes, we will highlight recent examples of metabolic and combinatorial engineering approaches successfully applied to the production of novel glycosylated compounds.
Keywords: Glycosylated Natural Products, anthracyclines, Macrolide antibiotics, spinosyns, chemotherapy, Bleomycins
Current Topics in Medicinal Chemistry
Title: Glycosyltransferases, Important Tools for Drug Design
Volume: 8 Issue: 8
Author(s): Andriy Luzhetskyy, Carmen Mendez, Jose A. Salas and Andreas Bechthold
Affiliation:
Keywords: Glycosylated Natural Products, anthracyclines, Macrolide antibiotics, spinosyns, chemotherapy, Bleomycins
Abstract: An increasing appreciation of carbohydrates as components of natural products has uncovered new opportunities in carbohydrate-based drug design. Glycosylated natural products produced by microorganisms contain a variety of different sugars. Usually the biosynthetic pathways to deoxysugars start from a monosacchride-1-phosphate which is converted to a NDP-hexose by a nucleotidyltransferase. Modification of this intermediate by different enzymes (e.g. dehydratases, epimerases, aminotransferases) yields the final sugar. In contrast to microorganisms, plant products mostly contain glucose, galactose, rhamnose and xylose as structural elements. In all organisms the nucleotide-activated sugar is attached to an aglycon by a glycosyltransferrase (GT). As no single universal GT has been uncovered yet, accomplishing the generation of novel glycosylated compounds requires a deep understanding of the function of glycosyltransferases (GTs) and its specificity. In this review we will present important drugs that contain sugar components. We will give an overview about the existing natural product GTs and we will discuss the structural features of GTs. Through specific examples within different compound classes, we will highlight recent examples of metabolic and combinatorial engineering approaches successfully applied to the production of novel glycosylated compounds.
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Cite this article as:
Luzhetskyy Andriy, Mendez Carmen, Salas A. Jose and Bechthold Andreas, Glycosyltransferases, Important Tools for Drug Design, Current Topics in Medicinal Chemistry 2008; 8 (8) . https://dx.doi.org/10.2174/156802608784221514
DOI https://dx.doi.org/10.2174/156802608784221514 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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