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Macrophage-activating lipopeptide 2 (MALP-2) is a lipopeptide Toll-like receptor (TLR)-2 and 6 agonist. It is used in immunological research to simulate Mycoplasma bacterial infections and activate immune cells. MALP-2 holds promise as a novel vaccine adjuvant due to its activation of TLRs.[1][2] It also promotes vascular, bone, and wound healing.[3][4]

Structure

MALP-2 has the structure S-2,3-bis(palmityloxy)-(2R)-propyl-cysteinyl-GNNDESNISFKEK and is a post-translationally modified CGNNDESNISFKEK peptide in which in the N-terminus cysteine residue sidechain is linked to a diacylglycerol moiety where the two acyl groups are both derived from palmitic acid.[5]

Discovery

MALP-2 was initially named mycoplasma-derived high-molecular-weight material (MDHM) and, as the name suggests, had originally been isolated from Mycoplasma fermentans as an amphiphilic molecule with macropage-activating properties. This discovery helped explain how Mycoplasma bacteria can provoke immune responses despite lacking a cell wall.[6][7]

References

  1. ^ Hamley IW (August 2021). "Lipopeptides for Vaccine Development". Bioconjugate Chemistry. 32 (8): 1472–1490. doi:10.1021/acs.bioconjchem.1c00258. PMC 8382226. PMID 34228433.
  2. ^ Moyle PM, Toth I (2008). "Self-adjuvanting lipopeptide vaccines". Current Medicinal Chemistry. 15 (5): 506–516. doi:10.2174/092986708783503249. PMID 18289006.
  3. ^ Liao D, Su X, Wang J, Yu J, Luo H, Tian W, et al. (January 2023). "Pushing the envelope: Immune mechanism and application landscape of macrophage-activating lipopeptide-2". Frontiers in Immunology. 14: 1113715. doi:10.3389/fimmu.2023.1113715. PMC 9902699. PMID 36761746.
  4. ^ Knorr C, Hübschle T, Murgott J, Mühlradt P, Gerstberger R, Roth J (April 2008). "Macrophage-activating lipopeptide-2 (MALP-2) induces a localized inflammatory response in rats resulting in activation of brain sites implicated in fever". Brain Research. 1205: 36–46. doi:10.1016/j.brainres.2008.02.021. PMID 18353287. S2CID 206317405.
  5. ^ "MALP-2". Enzo Life Sciences, Inc.
  6. ^ Mühlradt PF, Frisch M (September 1994). "Purification and partial biochemical characterization of a Mycoplasma fermentans-derived substance that activates macrophages to release nitric oxide, tumor necrosis factor, and interleukin-6". Infection and Immunity. 62 (9): 3801–3807. doi:10.1128/iai.62.9.3801-3807.1994. PMC 303034. PMID 8063396.
  7. ^ Mühlradt PF, Kiess M, Meyer H, Süssmuth R, Jung G (June 1997). "Isolation, structure elucidation, and synthesis of a macrophage stimulatory lipopeptide from Mycoplasma fermentans acting at picomolar concentration". The Journal of Experimental Medicine. 185 (11): 1951–8. doi:10.1084/jem.185.11.1951. PMC 2196331. PMID 9166424.
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