<i>ortho</i>-Substituted lipidated Brartemicin derivative shows promising Mincle-mediated adjuvant activity

Foster, Amy J.; Kodar, Kristel; Timmer, Mattie S. M.; Stocker, Bridget L.

doi:10.1039/c9ob02397f

Cited by 24 publications

(13 citation statements)

References 53 publications

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“…Brartemicin, a glycosyl glycoside derivative isolated from Nonomuraea species with similarity in structure to TDB, was originally identified for its antitumor activities and is also recognized by Mincle [ 109 , 115 ]. Lipidated Brartemicin analogues and especially the o ‐substituted variant showed strong inflammatory activities, inducing Mincle signaling and pro‐inflammatory cytokine responses in both mouse bone marrow‐derived macrophages and human monocytes [ 116 , 117 ].…”

Section: New Glyco‐based Strategies To Steer Immune Responses In Infection Cancer and Autoimmunitymentioning

confidence: 99%

Emerging glyco‐based strategies to steer immune responses

et al. 2021

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Glycan structures are common posttranslational modifications of proteins, which serve multiple important structural roles (for instance in protein folding), but also are crucial participants in cell–cell communications and in the regulation of immune responses. Through the interaction with glycan‐binding receptors, glycans are able to affect the activation status of antigen‐presenting cells, leading either to induction of pro‐inflammatory responses or to suppression of immunity and instigation of immune tolerance. This unique feature of glycans has attracted the interest and spurred collaborations of glyco‐chemists and glyco‐immunologists to develop glycan‐based tools as potential therapeutic approaches in the fight against diseases such as cancer and autoimmune conditions. In this review, we highlight emerging advances in this field, and in particular, we discuss on how glycan‐modified conjugates or glycoengineered cells can be employed as targeting devices to direct tumor antigens to lectin receptors on antigen‐presenting cells, like dendritic cells. In addition, we address how glycan‐based nanoparticles can act as delivery platforms to enhance immune responses. Finally, we discuss some of the latest developments in glycan‐based therapies, including chimeric antigen receptor (CAR)‐T cells to achieve targeting of tumor‐associated glycan‐specific epitopes, as well as the use of glycan moieties to suppress ongoing immune responses, especially in the context of autoimmunity.

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Section: New Glyco‐based Strategies To Steer Immune Responses In Infection Cancer and Autoimmunitymentioning

confidence: 99%

Emerging glyco‐based strategies to steer immune responses

et al. 2021

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“…C 8 GlcC 8 This work builds on related efforts exploring structure activity relationships of acyl-hexoses (as analogues of glucose monomycolate), 15,16 glycosyloxy-stearates (as analogues of the mannosyloxymannitol glycolipid from Malassezia pachydermatis), 28 glycerolipids (as analogues of glycerol monomycolate), 27,29 mono- 13 and diacyl trehaloses, 12,30 and lipidated diaroyltrehaloses (as analogues of brartemicin). 14,31 The present work is notable for the simplicity of the resulting agonists and the fact that unlike acyl-hexoses they exist as single stereoisomers.…”

Section: Nfat-gfp (%)mentioning

confidence: 99%

Design of Potent Mincle Signalling Agonists Based on an Alkyl b- Glucoside Template

SMITH¹,

Hosono²,

Nagata³

et al. 2020

Preprint

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“…[3] Notably, TDB has been applied to a cationic liposomal system CAF01, [8] which was evaluated in human clinical trials against tuberculosis and HIV. [9,10] Various Mincle ligands have been reported including the glycolipids such as 6-acylated glycosides, [11] glucosyl diacylglycerides, [12][13][14] other trehalose esters, [15][16][17][18][19][20][21][22][23][24] and also recently found cholesteryl acyl α-glucosides (αCAG). [25][26][27] We previously reported that 1-monoacylglycerol harbors relationships between activity and acyl chain length.…”

Section: Introductionmentioning

confidence: 99%

Fungal β‐Mannosyloxymannitol Glycolipids and Their Analogues: Synthesis and Mincle‐Mediated Signaling Activity

et al. 2022

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Mincle, a C-type lectin receptor (CLR), senses certain lipid conjugates, leading to the activation of the innate immune system. The lipid conjugate ligands include glyco-, glycero-, and mannitol lipids. Recently, a fungal β-mannosyloxymannitol glycolipid demonstrating a novel architecture, "44-2," was isolated from the fungus Malassezia and displayed potent Mincle-mediated signaling activity. For this study, we synthe-sized the diastereomeric pair of mannosyloxymannitol glycolipids and their analogues and analyzed the structure-activity relationships of Mincle-mediated signaling. The results suggest that the dimannosyl-fatty acid moiety in the mannosyloxymannitol glycolipid-type structure plays a major role in the molecular recognition of Mincle.

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ortho-Substituted lipidated Brartemicin derivative shows promising Mincle-mediated adjuvant activity

Abstract: Structure activity relationship studies of lipidated Brartemicin analogues have revealed the potent adjuvant activity of ortho-substituted Brartemicin analogue 5a, which was better than that of p-OC18 (5c) and C18dMeBrar (4).

Cited by 24 publications

References 53 publications

Emerging glyco‐based strategies to steer immune responses

Emerging glyco‐based strategies to steer immune responses

Design of Potent Mincle Signalling Agonists Based on an Alkyl b- Glucoside Template

Fungal β‐Mannosyloxymannitol Glycolipids and Their Analogues: Synthesis and Mincle‐Mediated Signaling Activity

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