Abstract
A Natural Compound Library containing myxobacterial secondary metabolites was screened in murine macrophages for novel activators of IL-1/beta maturation and secretion. The most potent of three hits in total was a so far undescribed metabolite, which was identified from the myxobacterium Hyalangium minutum strain Hym3. While the planar structure of 1 was elucidated by high resolution mass spectrometry and NMR data yielding an asymmetric boron containing a macrodiolide core structure, its relative stereochemistry of all 20 stereocenters of the 42-membered ring was assigned by rotating frame Overhause effect spectroscopy correlations, H-1,H-1, and H-1,C-13 coupling constants, and by comparison of C-13 chemical shifts to those of the structurally related metabolites tartrolon B-D. The absolute stereochemistry was subsequently assigned by Mosher's and Marfey's methods. Further functional studies revealed that hyaboron and other boronated natural compounds resulted in NLRP3 inflammasome dependent IL-1/beta maturation, which is most likely due to their ability to act as potassium ionophores. Moreover, besides its inflammasome-stimulatory activity in human and mouse cells, hyaboron (1) showed additional diverse biological activities, including antibacterial and antiparasitic effects.
| Item Type: | Journal article |
|---|---|
| Faculties: | Chemistry and Pharmacy > Department of Biochemistry |
| Research Centers: | Center for Integrated Protein Science Munich (CIPSM) |
| Subjects: | 500 Science > 540 Chemistry |
| ISSN: | 1554-8929 |
| Language: | English |
| Item ID: | 68170 |
| Date Deposited: | 19. Jul 2019, 12:24 |
| Last Modified: | 04. Nov 2020, 13:50 |
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