Advances in Desmuramyl Peptide Research

Ribić, Rosana; Paurević, Marija; Tomić, Srđanka

doi:10.5562/cca3556

Cited by 4 publications

(2 citation statements)

References 62 publications

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“…4b MDP congeners without the sugar moiety (MurNAc) are usually referred to as desmuramyl peptides (DMPs). 9 Several DMPs have revealed remarkable antitumor potency and noteworthy immunomodulatory activities, as exemplified by DMP-Paclitaxel conjugates. 10 It is evident from a number of examples that the sugar unit can be substituted with acyl groups or derivatized without affecting its immunological activity, as epitomized by LK-409, LK-415, LK-423, many carbocyclic analogues of MDP, 7-(oxoacyl)- l -alanyl- d -isoglutamine and other adamantyl-substituted MDP congeners.…”

Section: Table 1 Optimization Of the Reaction Condition...mentioning

confidence: 99%

A Robust, Gram-Scale and High-Yield Synthesis of MDP Congeners for Activation of the NOD2 Receptor and Vaccine Adjuvantation

et al. 2022

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Bacterial peptidoglycan (PGN) constituent – muramyl dipeptide (MDP) and its congeners possess immuno-adjuvant activity, and find their applications in vaccines to potentiate the immune response of antigens. The molecule confers non-specific resistance to pathogenic infections and defense against tumors. In this work, the parent MDP molecule was re-designed by replacing its carbohydrate moiety with an immunoregulatory xanthine scaffold, while conserving L-D configuration of the pharmacophore. Alkyl chains were introduced at the C-terminus of D-isoglutamine to help the molecules access cytoplasmic NOD2 receptor and activate the innate immune system. Lipophilic MDP congeners were thus obtained by adopting a direct or indirect convergent synthetic route with an overall yield of > 50 %. We found that an indirect approach can be reliably implemented on a gram-scale, thereby unlocking access to substantial amounts of pathogen associated molecular patterns for in vivo studies, which will accelerate the development of NOD2 immuno-adjuvants against viral and bacterial infections.

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Section: Table 1 Optimization Of the Reaction Condition...mentioning

confidence: 99%

A Robust, Gram-Scale and High-Yield Synthesis of MDP Congeners for Activation of the NOD2 Receptor and Vaccine Adjuvantation

et al. 2022

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“…PGN fragments such as muramyl peptides 83 activate the immune system through induction of the NLR pathway, i.e., molecular recognition by intracellular NOD-like receptors. Their activity can be enhanced by other types of PRR, such as toll-like receptor (TLR) activation.…”

Section: ■ Conclusionmentioning

confidence: 99%

Targeted Delivery of Adamantylated Peptidoglycan Immunomodulators in Lipid Nanocarriers: NMR Shows That Cargo Fragments Are Available on the Surface

et al. 2020

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We present an in-depth investigation of the membrane interactions of peptidoglycan (PGN)-based immune adjuvants designed for lipid-based delivery systems using NMR spectroscopy. The derivatives contain a cargo peptidoglycan (PGN) dipeptide fragment and an adamantyl group, which serves as an anchor to the lipid bilayer. Furthermore, derivatives with a mannose group that can actively target cell surface receptors on immune cells are also studied. We showed that the targeting mannose group and the cargo PGN fragment are both available on the lipid bilayer surface, thereby enabling interactions with cognate receptors. We found that the nonmannosylated compounds are incorporated stronger into the lipid assemblies than the mannosylated ones, but the latter compounds penetrate deeper in the bilayer. This might be explained by stronger electrostatic interactions available for zwitterionic nonmannosylated derivatives as opposed to the compounds in which the charged N-terminus is capped by mannose groups. The higher incorporation efficiency of the nonmannosylated compounds correlated with a larger relative enhancement in immune stimulation activities upon lipid incorporation compared to that of the derivatives with the mannose group. The chirality of the adamantyl group also influenced the incorporation efficiency, which in turn correlated with membrane-associated conformations that affect possible intermolecular interactions with lipid molecules. These findings will help in improving the development of PGN-based immune adjuvants suitable for delivery in lipid nanoparticles.

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Amphiphilic desmuramyl peptides for the rational design of new vaccine adjuvants: Synthesis, in vitro modulation of inflammatory response and molecular docking studies

Khan

Nasim

Wang

et al. 2021

European Journal of Medicinal Chemistry

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Advances in Desmuramyl Peptide Research

Cited by 4 publications

References 62 publications

A Robust, Gram-Scale and High-Yield Synthesis of MDP Congeners for Activation of the NOD2 Receptor and Vaccine Adjuvantation

A Robust, Gram-Scale and High-Yield Synthesis of MDP Congeners for Activation of the NOD2 Receptor and Vaccine Adjuvantation

Targeted Delivery of Adamantylated Peptidoglycan Immunomodulators in Lipid Nanocarriers: NMR Shows That Cargo Fragments Are Available on the Surface

Amphiphilic desmuramyl peptides for the rational design of new vaccine adjuvants: Synthesis, in vitro modulation of inflammatory response and molecular docking studies

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