Total synthesis of the Mycobacterium tuberculosis dideoxymycobactin-838 and stereoisomers: Diverse CD1a-restricted T cells display a common hierarchy of lipopeptide recognition

Cheng, Janice, Liu, Ligong, Pellicci, Daniel, Reddiex, Scott J.J., Cotton, Rachel, Cheng, Tan-Yun, Young, David, Van Rhijn, Ildiko, Moody, Branch, Rossjohn, Jamie, Fairlie, David, Godfrey, Dale and Williams, Spencer John (2017) Total synthesis of the Mycobacterium tuberculosis dideoxymycobactin-838 and stereoisomers: Diverse CD1a-restricted T cells display a common hierarchy of lipopeptide recognition. Chemistry - A European Journal, 23 7: 1694-1701. doi:10.1002/chem.201605287


Author Cheng, Janice
Liu, Ligong
Pellicci, Daniel
Reddiex, Scott J.J.
Cotton, Rachel
Cheng, Tan-Yun
Young, David
Van Rhijn, Ildiko
Moody, Branch
Rossjohn, Jamie
Fairlie, David
Godfrey, Dale
Williams, Spencer John
Title Total synthesis of the Mycobacterium tuberculosis dideoxymycobactin-838 and stereoisomers: Diverse CD1a-restricted T cells display a common hierarchy of lipopeptide recognition
Journal name Chemistry - A European Journal   Check publisher's open access policy
ISSN 0947-6539
1521-3765
Publication date 2017-01-01
Sub-type Article (original research)
DOI 10.1002/chem.201605287
Open Access Status Not yet assessed
Volume 23
Issue 7
Start page 1694
End page 1701
Total pages 9
Place of publication Weinheim, Germany
Publisher Wiley
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
 
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Created: Thu, 05 Jan 2017, 01:59:14 EST by Susan Allen on behalf of Institute for Molecular Bioscience