MS/MS fragmentation-guided search of TMG-chitooligomycins and their structure-activity relationship in specific β-N-acetylglucosaminidase inhibition.
In: Organic & biomolecular chemistry, Jg. 9 (2011-04-21), Heft 8, S. 2943-51
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Zugriff:
The reducing tetrasaccharide TMG-chitotriomycin (1) is an inhibitor of β-N-acetylglucosaminidase (GlcNAcase), produced by the actinomycete Streptomyces anulatus NBRC13369. The inhibitor shows a unique inhibitory spectrum, that is, selectivity toward enzymes from chitin-containing organisms such as insects and fungi. Nevertheless, its structure-selectivity relationship remains to be clarified. In this study, we conducted a structure-guided search of analogues of 1 in order to obtain diverse N,N,N-trimethylglucosaminium (TMG)-containing chitooligosaccharides. In this approach, the specific fragmentation profile of 1 on ESI-MS/MS analysis was used for the selective detection of desired compounds. As a result, two new analogues, named TMG-chitomonomycin (3) and TMG-chitobiomycin (2), were obtained from a culture filtrate of 1-producing Streptomyces. Their enzyme-inhibiting activity revealed that the potency and selectivity depended on the degree of polymerization of the reducing end GlcNAc units. Furthermore, a computational modeling study inspired the inhibitory mechanism of TMG-related compounds as a mimic of the substrate in the Michaelis complex of the GH20 enzyme. This study is an example of the successful application of a MS/MS experiment for structure-guided isolation of natural products.
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MS/MS fragmentation-guided search of TMG-chitooligomycins and their structure-activity relationship in specific β-N-acetylglucosaminidase inhibition.
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Autor/in / Beteiligte Person: | Usuki, H ; Yamamoto, Y ; Kumagai, Y ; Nitoda, T ; Kanzaki, H ; Hatanaka, T |
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Zeitschrift: | Organic & biomolecular chemistry, Jg. 9 (2011-04-21), Heft 8, S. 2943-51 |
Veröffentlichung: | Cambridge, UK : Royal Society of Chemistry, c2003-, 2011 |
Medientyp: | academicJournal |
ISSN: | 1477-0539 (electronic) |
DOI: | 10.1039/c0ob01090a |
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