Muramyl dipeptide explained

Muramyl dipeptide is a component of bacterial peptidoglycan, a recognition structure or activator for nucleotide-binding oligomerization domain 2 (NOD2) protein.^[1] It is a constituent of both Gram-positive and Gram-negative bacteria composed of N-acetylmuramic acid linked by its lactic acid moiety to the N-terminus of an L-alanine D-isoglutamine dipeptide. It can be recognized by the immune system as a pathogen-associated molecular pattern and activate the NALP3 inflammasome which, in turn, leads to cytokine activation, IL-1α and IL-1β especially.^[2]

Human NOD2 protein of the nucleotide-binding leucine-rich repeat family, is a cytoplasmic receptor involved in host innate immune system defense. Mutations in the CARD15 gene encoding NOD2 protein have been observed in Crohn's disease patients,^[3] decreasing the immune systems of these patients ability to recognize muramyl dipeptide. Analogues of muramyl dipeptide and their potential for immune response therapies in cancer and disease are being investigated.^[4] Experiments published in 2008 showed that muramyl dipeptide is involved in a molecular pathway in mice that conferred protection from colitis.^[5]

See also

• Taxol
• Dipeptide
• Mifamurtide, a synthetic analogue for the treatment of osteosarcoma

Notes and References

1. Inohara N, Ogura Y, Fontalba A, Gutierrez O, Pons F, Crespo J, Fukase K, Inamura S, Kusumoto S, Hashimoto M, Foster SJ, Moran AP, Fernandez-Luna JL, Nuñez G . 6 . Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn's disease . The Journal of Biological Chemistry . 278 . 8 . 5509–5512 . February 2003 . 12514169 . 10.1074/jbc.C200673200 . free . 10379/9336 . free .
2. Martinon F, Agostini L, Meylan E, Tschopp J . Identification of bacterial muramyl dipeptide as activator of the NALP3/cryopyrin inflammasome . Current Biology . 14 . 21 . 1929–1934 . November 2004 . 15530394 . 10.1016/j.cub.2004.10.027 . 13728991 . free .
3. Inohara N, Ogura Y, Fontalba A, Gutierrez O, Pons F, Crespo J, Fukase K, Inamura S, Kusumoto S, Hashimoto M, Foster SJ, Moran AP, Fernandez-Luna JL, Nuñez G . 6 . Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn's disease . The Journal of Biological Chemistry . 278 . 8 . 5509–5512 . February 2003 . 12514169 . 10.1074/jbc.c200673200 . free . 10379/9336 . free .
4. Li X, Yu J, Xu S, Wang N, Yang H, Yan Z, Cheng G, Liu G . 6 . Chemical conjugation of muramyl dipeptide and paclitaxel to explore the combination of immunotherapy and chemotherapy for cancer . Glycoconjugate Journal . 25 . 5 . 415–425 . July 2008 . 18161023 . 10.1007/s10719-007-9095-3 . 19058605 .
5. Watanabe T, Asano N, Murray PJ, Ozato K, Tailor P, Fuss IJ, Kitani A, Strober W . 6 . Muramyl dipeptide activation of nucleotide-binding oligomerization domain 2 protects mice from experimental colitis . The Journal of Clinical Investigation . 118 . 2 . 545–559 . February 2008 . 18188453 . 2176188 . 10.1172/JCI33145 .