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Total Synthesis of Mycobacterium tuberculosis Dideoxymycobactin-838 and Stereoisomers: Diverse CD1a-Restricted T Cells Display a Common Hierarchy of Lipopeptide Recognition.
- Source :
-
Chemistry - A European Journal . 1/31/2017, Vol. 23 Issue 7, p1694-1701. 8p. - Publication Year :
- 2017
-
Abstract
- Mycobacterium tuberculosis produces dideoxymycobactin-838 (DDM-838), a lipopeptide that potently activates T cells upon binding to the MHC-like antigen-presenting molecule CD1a. M. tuberculosis produces DDM-838 in only trace amounts and a previous solid-phase synthesis provided sub-milligram quantities. We describe a high-yielding solution-phase synthesis of DDM-838 that features a Mitsunobu substitution that avoids yield-limiting epimerization at lysine during esterification, and amidation conditions that prevent double-bond isomerization of the Z-C20:1 acyl chain, and provides material with equivalent antigenicity to natural DDM-838. Isomers of DDM-838 that varied in stereochemistry at the central lysine and the C20:1 acyl chain were compared for their ability to be recognised by CD1a-restricted T cell receptors (TCRs). These TCRs, derived from unrelated human donors, exhibited a similar spectrum of reactivity towards the panel of DDM-838 isomers, highlighting the exquisite sensitivity of lipopeptide-reactive T cells for the natural DDM stereochemistry. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09476539
- Volume :
- 23
- Issue :
- 7
- Database :
- Academic Search Index
- Journal :
- Chemistry - A European Journal
- Publication Type :
- Academic Journal
- Accession number :
- 121062201
- Full Text :
- https://doi.org/10.1002/chem.201605287