The Total Synthesis of Glycolipids from Streptococcus pneumoniae and a Re-evaluation of Their Immunological Activity.

Autor:	Sadraei SI; Department of Chemistry and Biochemistry, University of Windsor, ON N9B 3P4, Windsor, Canada., Yousif G; Department of Chemistry and Biochemistry, University of Windsor, ON N9B 3P4, Windsor, Canada., Taimoory SM; Department of Chemistry and Biochemistry, University of Windsor, ON N9B 3P4, Windsor, Canada.; Department of Chemistry, University of Michigan, 48109-1055, Ann Arbor, MI, USA., Kosar M; Department of Chemistry and Biochemistry, University of Windsor, ON N9B 3P4, Windsor, Canada., Mehri S; Department of Chemistry and Biochemistry, University of Windsor, ON N9B 3P4, Windsor, Canada., Alolabi R; Department of Biomedical Sciences, University of Windsor, ON N9B 3P4, Windsor, Canada., Igbokwe E; Department of Chemistry and Biochemistry, University of Windsor, ON N9B 3P4, Windsor, Canada., Toma J; Department of Biomedical Sciences, University of Windsor, ON N9B 3P4, Windsor, Canada., Rahim MMA; Department of Biomedical Sciences, University of Windsor, ON N9B 3P4, Windsor, Canada., Trant JF; Department of Chemistry and Biochemistry, University of Windsor, ON N9B 3P4, Windsor, Canada.
Jazyk:	angličtina
Zdroj:	Chembiochem : a European journal of chemical biology [Chembiochem] 2022 Sep 16; Vol. 23 (18), pp. e202200361. Date of Electronic Publication: 2022 Jul 27.
DOI:	10.1002/cbic.202200361
Abstrakt:	Invariant natural killer (iNK) T cells, Type I iNKTs, are responsible for the production of pro-inflammatory cytokines which induce a systemic immune response. They are distinctive in possessing an semi-invariant T-cell receptor that recognizes glycolipid antigens presented by CD1d, a protein closely related to the class I major histocompatibility complex, conserved across multiple mammalian species in a class of proteins well-renowned for their high degree of polymorphism. This receptor's first potent identified antigen is the α-galactosylceramide, KRN7000, a synthetic glycosphingolipid closely related to those isolated from bacteria that were found on a Japanese marine sponge. A corresponding terrestrial antigen remained unidentified until two specific diacylglycerol-containing glycolipids, reported to activate iNKT cells, were isolated from Streptococcus pneumoniae. We report the total synthesis and immunological re-evaluation of these two glycolipids. The compounds are unable to meaningfully activate iNKT cells. Computational modelling shows that these ligands, while being capable of interacting with the CD1d receptor, create a different surface for the binary complex that makes formation of the ternary complex with the iNKT T-cell receptor difficult. Together these results suggest that the reported activity might have been due to an impurity in the original isolated sample and highlights the importance of taking care when reporting biological activity from isolated natural products. (© 2022 Wiley-VCH GmbH.)
Databáze:	MEDLINE
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