Lipid structure influences the ability of glucose monocorynomycolate to signal through Mincle

Phillip L. Van Der Peet, Masahiro Nagata, Sayali Shah, Jonathan M. White, Sho Yamasaki, Spencer J. Williams

    Research output: Contribution to journalArticle

    8 Citations (Scopus)

    Abstract

    Mincle (macrophage-inducible C-type lectin) is a C-type lectin receptor that provides the capacity for immune sensing of a range of pathogen- and commensal-derived glycolipids. Mincle can recognize mycolic and/or corynomycolic acid esters of trehalose, glycerol and glucose from mycobacteria and corynebacteria. While simple straight-chain long fatty acids (e.g. behenic acid) can substitute for mycolic acid on trehalose and glycerol and maintain robust signalling through Mincle, glucose monobehenate has been reported to be much less active than glucose monocorynomycolate (GMCM). We report the preparation of a range of analogues of GMCM to explore structural requirements in the lipid chain for signalling through Mincle. GMCM analogues bearing simple straight chain or branched fatty acid esters provided only weak signalling through human and mouse Mincle. A GMCM variant with a truncated (pentyl) α-chain provided attenuated signalling, whereas an analogue with an extended (tricosyl; C23) α-chain signalled as potently as GMCM. This work suggests that Mincle has the ability to survey mycolate-derived glycolipids from actinomycetes, distinguishing non-pathogenic (e.g. Rhodococcus spp.) and pathogenic (e.g. Mycobacterium tuberculosis) species on the basis of α-chain length. Finally, an α-phenyldodecyl analogue of GMCM possessed similar potency to GMCM and was only slightly less potent than trehalose dimycolate (cord factor), showing that large functional groups may be tolerated in the α-chain.

    Original languageEnglish
    Pages (from-to)9267-9277
    Number of pages11
    JournalOrganic and Biomolecular Chemistry
    Volume14
    Issue number39
    DOIs
    Publication statusPublished - Jan 1 2016

    Fingerprint

    C-Type Lectins
    macrophages
    Macrophages
    glucose
    lipids
    Lipids
    Glucose
    Cord Factors
    Mycolic Acids
    analogs
    Trehalose
    Glycolipids
    fatty acids
    glycerols
    Glycerol
    acids
    esters
    Esters
    actinomycetes
    Bearings (structural)

    All Science Journal Classification (ASJC) codes

    • Biochemistry
    • Physical and Theoretical Chemistry
    • Organic Chemistry

    Cite this

    Van Der Peet, P. L., Nagata, M., Shah, S., White, J. M., Yamasaki, S., & Williams, S. J. (2016). Lipid structure influences the ability of glucose monocorynomycolate to signal through Mincle. Organic and Biomolecular Chemistry, 14(39), 9267-9277. https://doi.org/10.1039/c6ob01781a

    Lipid structure influences the ability of glucose monocorynomycolate to signal through Mincle. / Van Der Peet, Phillip L.; Nagata, Masahiro; Shah, Sayali; White, Jonathan M.; Yamasaki, Sho; Williams, Spencer J.

    In: Organic and Biomolecular Chemistry, Vol. 14, No. 39, 01.01.2016, p. 9267-9277.

    Research output: Contribution to journalArticle

    Van Der Peet, PL, Nagata, M, Shah, S, White, JM, Yamasaki, S & Williams, SJ 2016, 'Lipid structure influences the ability of glucose monocorynomycolate to signal through Mincle', Organic and Biomolecular Chemistry, vol. 14, no. 39, pp. 9267-9277. https://doi.org/10.1039/c6ob01781a
    Van Der Peet, Phillip L. ; Nagata, Masahiro ; Shah, Sayali ; White, Jonathan M. ; Yamasaki, Sho ; Williams, Spencer J. / Lipid structure influences the ability of glucose monocorynomycolate to signal through Mincle. In: Organic and Biomolecular Chemistry. 2016 ; Vol. 14, No. 39. pp. 9267-9277.
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