Asymmetric Total Synthesis and Structural Revision of DAT2, an Antigenic Glycolipid from Mycobacterium tuberculosis.
Angew Chem Int Ed Engl
; 63(19): e202318582, 2024 05 06.
Article
in En
| MEDLINE
| ID: mdl-38456226
ABSTRACT
DAT2 is a member of the diacyl trehalose family (DAT) of antigenic glycolipids located in the mycomembrane of Mycobacterium tuberculosis (Mtb). Recently it was shown that the molecular structure of DAT2 had been incorrectly assigned, but the correct structure remained elusive. Herein, the correct molecular structure of DAT2 and its methyl-branched acyl substituent mycolipanolic acid is determined. For this, four different stereoisomers of mycolipanolic acid were prepared in a stereoselective and unified manner, and incorporated into DAT2. A rigorous comparison of the four isomers to the DAT isolated from Mtb H37Rv by NMR, HPLC, GC, and mass spectrometry allowed a structural revision of mycolipanolic acid and DAT2. Activation of the macrophage inducible Ca2+-dependent lectin receptor (Mincle) with all four stereoisomers shows that the natural stereochemistry of mycolipanolic acid / DAT2 provides the strongest activation, which indicates its high antigenicity and potential application in serodiagnostics and vaccine adjuvants.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Glycolipids
/
Mycobacterium tuberculosis
Language:
En
Journal:
Angew Chem Int Ed Engl
Year:
2024
Document type:
Article
Affiliation country:
Netherlands
Country of publication:
Germany