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Incorporation of glucose analogs by GtfE and GtfD from the vancomycin biosynthetic pathway to generate variant glycopeptides
- Source :
- Chemistrybiology. 9(12)
- Publication Year :
- 2002
-
Abstract
- Analogs of the glycopeptide antibiotics vancomycin and teicoplanin with alterations in one or both sugar moieties of the disaccharide have been prepared by tandem action of the vancomycin pathway glycosyltransferases GtfE and GtfD. All four regioisomers (2-, 3-, 4-, 6-) of TDP-deoxyglucoses and UDP/TDP-aminoglucoses were prepared, predominantly by action of D-glucopyranosyl-1-phosphate thymidylyltransferase, E p . GtfE transferred the deoxyglucoses or aminoglucoses onto the 4-OH of 4-hydroxyphenylglycine of both the vancomycin and teicoplanin aglycone scaffolds. Kinetic analysis indicated the 2-, 3-, 4-, and 6-amino-glucoses were transferred by GtfE with only a 4- to 30-fold drop in k cat and no effect on K m compared to the native substrate, UDP/TDP-glucose, suggesting preparative utility. The next enzyme, GtfD, could utilize the variant glucosyl-peptides as substrates for transfer of L-4- epi -vancosamine. The aminosugar moieties in these variant glycopeptides introduce sites for acylation or reductive alkylation.
- Subjects :
- Stereochemistry
Clinical Biochemistry
Disaccharide
010402 general chemistry
01 natural sciences
Biochemistry
Substrate Specificity
Acylation
03 medical and health sciences
chemistry.chemical_compound
Vancomycin
Drug Discovery
Glycosyltransferase
medicine
Combinatorial Chemistry Techniques
Molecular Biology
030304 developmental biology
Pharmacology
chemistry.chemical_classification
0303 health sciences
biology
Molecular Structure
Teicoplanin
Glycopeptides
General Medicine
Glycopeptide
0104 chemical sciences
Anti-Bacterial Agents
carbohydrates (lipids)
Glycorandomization
Kinetics
Enzyme
Glucose
chemistry
Aminosugar
Glucosyltransferases
biology.protein
Molecular Medicine
medicine.drug
Subjects
Details
- ISSN :
- 10745521
- Volume :
- 9
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Chemistrybiology
- Accession number :
- edsair.doi.dedup.....057d00d30843d11b654ea86ed33d1859