Macrophage-activating lipopeptide 2 explained

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]

Notes and References

  1. Hamley IW . Lipopeptides for Vaccine Development . Bioconjugate Chemistry . 32 . 8 . 1472–1490 . August 2021 . 34228433 . 8382226 . 10.1021/acs.bioconjchem.1c00258 .
  2. Moyle PM, Toth I . Self-adjuvanting lipopeptide vaccines . Current Medicinal Chemistry . 2008 . 15 . 5 . 506–516 . 18289006 . 10.2174/092986708783503249 .
  3. Liao D, Su X, Wang J, Yu J, Luo H, Tian W, Ye Z, He J . 6 . Pushing the envelope: Immune mechanism and application landscape of macrophage-activating lipopeptide-2 . Frontiers in Immunology . 14 . 1113715 . January 2023 . 36761746 . 9902699 . 10.3389/fimmu.2023.1113715 . free .
  4. Knorr C, Hübschle T, Murgott J, Mühlradt P, Gerstberger R, Roth J . 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 . April 2008 . 18353287 . 10.1016/j.brainres.2008.02.021 . 206317405 .
  5. Web site: MALP-2 . Enzo Life Sciences, Inc. .
  6. Mühlradt PF, Frisch M . 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 . September 1994 . 8063396 . 303034 . 10.1128/iai.62.9.3801-3807.1994 .
  7. Mühlradt PF, Kiess M, Meyer H, Süssmuth R, Jung G . 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 . June 1997 . 9166424 . 2196331 . 10.1084/jem.185.11.1951 .

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