Identification of Neuroprotective Spoxazomicin and Oxachelin Glycosides via Chemoenzymatic Glycosyl-Scanning
| Autor: | Manjula Sunkara, Jon S. Thorson, Yinan Zhang, Samantha A. Scott, Sherif I. Elshahawi, Ryan R. Hughes, Larissa V. Ponomareva, Jianjun Zhang, Khaled A. Shaaban, Andrew J. Morris, Meredith A. Saunders, Mark A. Prendergast, Sydney R. Winchester |
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| Rok vydání: | 2016 |
| Předmět: |
Antifungal Agents
Glycosylation Stereochemistry Metabolite Pharmaceutical Science 010402 general chemistry 01 natural sciences Streptomyces Neuroprotection Article Analytical Chemistry Spoxazomicin C chemistry.chemical_compound Drug Discovery Glycosyltransferase Glycosyl Glycosides Oxazoles Pharmacology chemistry.chemical_classification Molecular Structure biology 010405 organic chemistry Chemistry Organic Chemistry Glycoside biology.organism_classification 0104 chemical sciences Neuroprotective Agents Complementary and alternative medicine Biochemistry biology.protein Molecular Medicine Oligopeptides |
| Zdroj: | Journal of Natural Products. 80:12-18 |
| ISSN: | 1520-6025 0163-3864 |
| DOI: | 10.1021/acs.jnatprod.6b00949 |
| Popis: | The assessment of glycosyl-scanning to expand the molecular and functional diversity of metabolites from the underground coal mine fire-associated Streptomyces sp. RM-14-6 is reported. Using the engineered glycosyltransferase OleD Loki and a 2-chloro-4-nitrophenylglycoside-based screen, six metabolites were identified as substrates of OleD Loki, from which 12 corresponding metabolite glycosides were produced and characterized. This study highlights the first application of the 2-chloro-4-nitrophenylglycoside-based screen toward an unbiased set of unique microbial natural products and the first reported application of the 2-chloro-4-nitrophenylglycoside-based transglycosylation reaction for the corresponding preparative synthesis of target glycosides. Bioactivity analysis (including antibacterial, antifungal, anticancer, and EtOH damage neuroprotection assays) revealed glycosylation to attenuate the neuroprotective potency of 4, while glycosylation of the structurally related inactive spoxazomicin C (3) remarkably invoked neuroprotective activity. |
| Databáze: | OpenAIRE |
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