Glycerol mycolates from synthetic mycolic acids

Ali, Omar T.; Sahb, Mohaned M.; Dulayymi, Juma’a R. Al; Baird, Mark S.

doi:10.1016/j.carres.2017.04.023

Cited by 8 publications

(8 citation statements)

References 35 publications

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“… Structures of synthetic glycerol monoesters that have been evaluated as macrophage inducible C-type lectin (Mincle) ligands ( 27 , 47 , 84 , 85 ). Of these, 18a , 18b , 18c , 19k , and 20k have been determined to be agonists for human Mincle and not murine Mincle.…”

Section: Glyceridesmentioning

confidence: 99%

“…The synthesis of four mycolate esters of R -glycerol ( 19d , e , g , h , Figure 7 ) and five esters of S -glycerol ( 20e–g , i , j ) have been described very recently and based on their structural similarity to the known glycerol-containing Mincle agonists, these mycolate esters of glycerol were suggested to be Mincle ligands ( 85 ). In these studies, however, R -GroMMs 19d , e , g , h were unable to induce cytokine production by BMDCs, while no results for the S -isomers were reported.…”

Section: Glyceridesmentioning

confidence: 99%

“…In these studies, however, R -GroMMs 19d , e , g , h were unable to induce cytokine production by BMDCs, while no results for the S -isomers were reported. Notwithstanding, it has been suggested that such mycolate esters may play a key role in the stimulation of CD1b-restricted germline-encoded, mycolyl-reactive (GEM) T cells, a process that can also be modulated by the corresponding free mycolic acids ( 85 ).…”

Section: Glyceridesmentioning

confidence: 99%

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Identification and Biological Activity of Synthetic Macrophage Inducible C-Type Lectin Ligands

et al. 2018

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The macrophage inducible C-type lectin (Mincle) is a pattern recognition receptor able to recognize both damage-associated and pathogen-associated molecular patterns, and in this respect, there has been much interest in determining the scope of ligands that bind Mincle and how structural modifications to these ligands influence ensuing immune responses. In this review, we will present Mincle ligands of known chemical structure, with a focus on ligands that have been synthetically prepared, such as trehalose glycolipids, glycerol-based ligands, and 6-acylated glucose and mannose derivatives. The ability of the different classes of ligands to influence the innate, and consequently, the adaptive, immune response will be described, and where appropriate, structure–activity relationships within each class of Mincle ligands will be presented.

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Section: Glyceridesmentioning

confidence: 99%

Section: Glyceridesmentioning

confidence: 99%

Section: Glyceridesmentioning

confidence: 99%

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Identification and Biological Activity of Synthetic Macrophage Inducible C-Type Lectin Ligands

et al. 2018

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“…Mycolic Acid preparation and formulation MA and their sugar esters were prepared as described previously (32,(49)(50)(51)(52)(53)(54). Table S1 provides structural information.…”

Section: Immunohistochemistrymentioning

confidence: 99%

CD1b-restricted GEM T cell responses are modulated byMycobacterium tuberculosismycolic acid meromycolate chains

Chancellor

Tocheva

Cave-Ayland

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Tuberculosis, caused by Mycobacterium tuberculosis, remains a major human pandemic. Germline-encoded mycolyl lipid-reactive (GEM) T cells are donor-unrestricted and recognize CD1b-presented mycobacterial mycolates. However, the molecular requirements governing mycolate antigenicity for the GEM T cell receptor (TCR) remain poorly understood. Here, we demonstrate CD1b expression in tuberculosis granulomas and reveal a central role for meromycolate chains in influencing GEM-TCR activity. Meromycolate fine structure influences T cell responses in TB-exposed individuals, and meromycolate alterations modulate functional responses by GEM-TCRs. Computational simulations suggest that meromycolate chain dynamics regulate mycolate head group movement, thereby modulating GEM-TCR activity. Our findings have significant implications for the design of future vaccines that target GEM T cells. Mycobaterium tuberculosis | GEM T cells | CD1b | Mycolate lipids |

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“…In the case of GroMCM, the majority of the activity resides in the 2′ S -isomer ( 36 ). Baird and co-workers have prepared a series of 2′ R - and 2′ S -GroMMs bearing authentic α-, keto-, and methoxy-mycolic acids ( 51 ). Consistent with the results for the GroMCMs, the 2′ R -isomers did not show any significant effects in the stimulation of cytokines in BMDCs.…”

Section: Sensing Of Microbial Lipids From Pathogens and Commensalsmentioning

confidence: 99%

Sensing Lipids with Mincle: Structure and Function

Williams

2017

Front. Immunol.

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Mincle is a C-type lectin receptor that has emerged as an important player in innate immunity through its capacity to recognize a wide range of lipidic species derived from damaged/altered self and foreign microorganisms. Self-ligands include sterols (e.g., cholesterol), and β-glucosylceramides, and the protein SAP130, which is released upon cell death. Foreign lipids comprise those from both microbial pathogens and commensals and include glycerol, glucose and trehalose mycolates, and glycosyl diglycerides. A large effort has focused on structural variation of these ligands to illuminate the structure–activity relationships required for the agonism of signaling though Mincle and has helped identify key differences in ligand recognition between human and rodent Mincle. These studies in turn have helped identify new Mincle ligands, further broadening our understanding of the diversity of organisms and lipidic species recognized by Mincle. Finally, progress toward the development of Mincle agonists as vaccine adjuvants providing humoral and cell-mediated immunity with reduced toxicity is discussed.

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Glycerol mycolates from synthetic mycolic acids

Abstract: R- and S-Glycerol mycolates derived from single synthetic α-, keto- and methoxy-mycolic acids are described.

Cited by 8 publications

References 35 publications

Identification and Biological Activity of Synthetic Macrophage Inducible C-Type Lectin Ligands

Identification and Biological Activity of Synthetic Macrophage Inducible C-Type Lectin Ligands

CD1b-restricted GEM T cell responses are modulated byMycobacterium tuberculosismycolic acid meromycolate chains

Sensing Lipids with Mincle: Structure and Function

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