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Updated: Jul 18, 2026
13:06
Improved In-gel Reductive β-Elimination for Comprehensive O-linked and Sulfo-glycomics by Mass Spectrometry
Published on: November 20, 2014
Glyco-stripping and glyco-swapping
Charles E Melançon1, Christopher J Thibodeaux, Hung-wen Liu
1Department of Chemistry and Biochemistry, College of Pharmacy, University of Texas at Austin, Austin, Texas 78712, USA.
ACS Chemical Biology
|December 16, 2006
Summary
Researchers harnessed the reversible reactions of glycosyltransferases (GTs) to create over 70 novel calicheamicin analogues. This breakthrough in glycosylation methodology expands the diversity of natural products for bioactivity studies.
Area of Science:
- Biochemistry
- Natural Product Chemistry
- Enzymology
Background:
- Glycosyltransferases (GTs) are crucial enzymes catalyzing glycosylation reactions, vital for natural product biosynthesis, virulence, and cellular recognition.
- The sugar components of natural products significantly influence their biological activity, making the synthesis of diverse glycoforms highly valuable.
- Understanding the enzymatic mechanisms of GTs is key to developing new synthetic strategies.
Purpose of the Study:
- To investigate the reversibility of glycosyltransferase reactions involved in natural product biosynthesis.
- To develop novel methodologies for generating diverse glycoforms of natural products by exploiting GT reversibility.
- To synthesize a library of calicheamicin analogues with potential for varied bioactivity.
Main Methods:
- Enzymatic assays were designed to test the reversibility of selected glycosyltransferases.
- Sugar exchange reactions were employed to modify the glycan moiety of natural products.
- Aglycon exchange strategies were utilized to alter the non-sugar part of the glycosylated compounds.
- The synthesized compounds were characterized to confirm their structures and diversity.
Main Results:
- Several glycosyltransferases involved in natural product biosynthesis were confirmed to catalyze reversible reactions.
- The study successfully generated over 70 novel calicheamicin analogues using sugar and aglycon exchange strategies.
- The developed methods demonstrate a powerful approach for diversifying complex natural products.
Conclusions:
- The reversibility of glycosyltransferases offers a versatile platform for the combinatorial synthesis of natural product analogues.
- This work provides a significant advancement in the field of glycosylation chemistry, enabling access to a wide array of glycoforms.
- The generated calicheamicin analogues represent a valuable resource for exploring structure-activity relationships and discovering new therapeutic agents.
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