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Hierarchical and Programmable One-Pot Oligosaccharide Synthesis
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Enzymatic methods for glyco(diversification/randomization) of drugs and small molecules
Richard W Gantt1, Pauline Peltier-Pain, Jon S Thorson
1Pharmaceutical Sciences Division, School of Pharmacy, Wisconsin Center for Natural Products Research, University of Wisconsin-Madison, USA.
Natural Product Reports
|September 9, 2011
Summary
Glyco randomization and diversification uses enzymatic glycosylation to create drug analogs with varied carbohydrates. This review explores how glycosylation impacts drug properties and enzyme classes used in these strategies.
Area of Science:
- Medicinal Chemistry
- Biotechnology
- Enzymology
Background:
- Glycosylation is a key post-translational modification influencing protein function and drug properties.
- Diversifying drug scaffolds with carbohydrates can modulate pharmacokinetic and pharmacodynamic profiles.
- Enzymatic glycosylation offers a precise method for generating diverse carbohydrate-decorated drug analogs.
Purpose of the Study:
- To review glyco randomization and diversification strategies in drug discovery.
- To highlight the impact of glycosylation on drug properties.
- To discuss enzyme classes, substrate synthesis, and library generation in glycorandomization.
Main Methods:
- Literature review of glyco randomization and diversification techniques.
- Analysis of glycosyl-conjugating enzymes and their applications.
- Examination of substrate synthesis and library construction methodologies.
Main Results:
- Glycosylation significantly influences drug properties such as solubility, stability, and target binding.
- Various classes of glycosyl-conjugating enzymes are suitable for glyco randomization.
- Both wild-type and engineered enzymes facilitate the creation of diverse glycorandomized libraries.
Conclusions:
- Glyco randomization/diversification is a powerful approach for generating novel drug candidates.
- Enzymatic glycosylation provides a versatile platform for medicinal chemistry efforts.
- Understanding enzyme capabilities and substrate requirements is crucial for successful glycorandomized library synthesis.
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