Synthesis of Glycolipid Library Reminiscent of Mycobacterial Cell Wall Motif A and Its Significance by Microscopy

Abstract

The cell wall of Mycobacterium tuberculosis (MTb) is distinguished by its unique glycolipid composition, notably mycolyl arabinogalactan, which features Araf, Galf, and mycolic acid. The terminal portion of arabinogalactan (AG) is motif A, a pentaarabinofuranoside characterized by two β-1,2 linkages and one each of α-1,5 and α-1,3 linkages. The C5 positions of motif A are esterified with mycolic acids, further enriched by unusual cyclopropanes. In this study, we synthesized a diverse array of MTb cell wall glycolipids inspired by motif A and explored their self-assembly behavior using microscopy. This collection of glycolipids includes variations with α or β-(1→2, 3, or 5) Araf linkages in di-, tri-, tetra-, and penta-arabinofuranosides, esterified with saturated, doubly unsaturated, or cyclopropanated long-chain fatty acids. The TEM analysis of the resulting self-assemblies revealed that subtle modifications in the anomeric linkages, length of the glycan, and the presence or absence of cyclopropanes impacted the morphology of the self-assembled structures.