acetylmuramyl alanyl isoglutamine


Summary: Peptidoglycan immunoadjuvant originally isolated from bacterial cell wall fragments; also acts as pyrogen and may cause arthritis; stimulates both humoral and cellular immunity.

Top Publications

  1. Netea M, Ferwerda G, de Jong D, Jansen T, Jacobs L, Kramer M, et al. Nucleotide-binding oligomerization domain-2 modulates specific TLR pathways for the induction of cytokine release. J Immunol. 2005;174:6518-23 pubmed
    ..Thus, interaction between NOD2 and specific TLR pathways may represent an important modulatory mechanism of innate immune responses. ..
  2. Uehori J, Fukase K, Akazawa T, Uematsu S, Akira S, Funami K, et al. Dendritic cell maturation induced by muramyl dipeptide (MDP) derivatives: monoacylated MDP confers TLR2/TLR4 activation. J Immunol. 2005;174:7096-103 pubmed
    ..These findings infer that the essential minimal requirement for TLR2/4-mediated adjuvancy of BCG lies within a modified MDP. ..
  3. Peeters H, Bogaert S, Laukens D, Rottiers P, De Keyser F, Darfeuille Michaud A, et al. CARD15 variants determine a disturbed early response of monocytes to adherent-invasive Escherichia coli strain LF82 in Crohn's disease. Int J Immunogenet. 2007;34:181-91 pubmed
    ..For the first time, a functional defect was detected in single heterozygous carriers. These findings reflect the potential role of a genetically altered host response to disease-related bacteria in the pathogenesis of CD. ..
  4. van Heel D, Ghosh S, Butler M, Hunt K, Lundberg A, Ahmad T, et al. Muramyl dipeptide and toll-like receptor sensitivity in NOD2-associated Crohn's disease. Lancet. 2005;365:1794-6 pubmed
  5. Kim J, Omori E, Matsumoto K, Nunez G, Ninomiya Tsuji J. TAK1 is a central mediator of NOD2 signaling in epidermal cells. J Biol Chem. 2008;283:137-44 pubmed
  6. Inohara N, Ogura Y, Fontalba A, Gutierrez O, Pons F, Crespo J, et al. Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn's disease. J Biol Chem. 2003;278:5509-12 pubmed
    ..Because muramyl dipeptide is the essential structure of peptidoglycan required for adjuvant activity, these results also have implications for understanding adjuvant function and effective vaccine development. ..
  7. Girardin S, Boneca I, Viala J, Chamaillard M, Labigne A, Thomas G, et al. Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J Biol Chem. 2003;278:8869-72 pubmed
    ..Additionally, the characterization of Nod2 as the first pathogen-recognition molecule that detects MDP will help to unravel the well known biological activities of this immunomodulatory compound. ..
  8. Tanabe T, Chamaillard M, Ogura Y, Zhu L, Qiu S, Masumoto J, et al. Regulatory regions and critical residues of NOD2 involved in muramyl dipeptide recognition. EMBO J. 2004;23:1587-97 pubmed
    ..These results provide new insights into the molecular function and regulation of NOD2 and related NOD family proteins. ..
  9. Kobayashi K, Chamaillard M, Ogura Y, Henegariu O, Inohara N, Nunez G, et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science. 2005;307:731-4 pubmed
    ..The Nod2 protein is thus a critical regulator of bacterial immunity within the intestine, providing a possible mechanism for Nod2 mutations in CD. ..

More Information


  1. Martinon F, Agostini L, Meylan E, Tschopp J. Identification of bacterial muramyl dipeptide as activator of the NALP3/cryopyrin inflammasome. Curr Biol. 2004;14:1929-34 pubmed
    ..The activation of the NALP3-inflammasome by MDP may be the basis of the potent adjuvant activity of MDP. ..
  2. Netea M, Ferwerda G, de Jong D, Werts C, Boneca I, Jehanno M, et al. The frameshift mutation in Nod2 results in unresponsiveness not only to Nod2- but also Nod1-activating peptidoglycan agonists. J Biol Chem. 2005;280:35859-67 pubmed
    ..Together, our results identified a cross-talk between the Nod1 and Nod2 pathways and suggested that down-regulation of Nod1/M-Tri(DAP) pathway may be associated with Crohn disease. ..
  3. Kobayashi K, Eynon E, Flavell R. Intracellular debugging. Nat Immunol. 2003;4:652-4 pubmed
  4. Yang Y, Yin C, Pandey A, Abbott D, Sassetti C, Kelliher M. NOD2 pathway activation by MDP or Mycobacterium tuberculosis infection involves the stable polyubiquitination of Rip2. J Biol Chem. 2007;282:36223-9 pubmed
    ..tuberculosis-induced Rip2 polyubiquitination appears MyD88-independent. Collectively, these data reveal that the NOD2 pathway is ubiquitin-regulated and that Rip2 employs a ubiquitin-dependent mechanism to achieve NF-kappaB activation. ..
  5. Inamura S, Fujimoto Y, Kawasaki A, Shiokawa Z, Woelk E, Heine H, et al. Synthesis of peptidoglycan fragments and evaluation of their biological activity. Org Biomol Chem. 2006;4:232-42 pubmed
    ..Here we reveal that TLR2 was not stimulated by the series of synthetic PG partial structures, whereas Nod2 recognizes the partial structures containing the MDP moiety. ..
  6. Wolfert M, Murray T, Boons G, Moore J. The origin of the synergistic effect of muramyl dipeptide with endotoxin and peptidoglycan. J Biol Chem. 2002;277:39179-86 pubmed
    ..Successful treatment of patients having mixed bacterial infections is likely to require interventions that address the mechanisms involved in responses induced by a variety of bacterial cell wall components. ..
  7. Kramer M, Netea M, de Jong D, Kullberg B, Adema G. Impaired dendritic cell function in Crohn's disease patients with NOD2 3020insC mutation. J Leukoc Biol. 2006;79:860-6 pubmed
    ..These data indicate that the NOD2fs mutation results in a loss-of-function phenotype in human myeloid DC and imply decreased immune regulation by IL-10 as a possible mechanism for this mutation in CD. ..
  8. Tada H, Aiba S, Shibata K, Ohteki T, Takada H. Synergistic effect of Nod1 and Nod2 agonists with toll-like receptor agonists on human dendritic cells to generate interleukin-12 and T helper type 1 cells. Infect Immun. 2005;73:7967-76 pubmed
    ..These findings suggest that Nod1 and Nod2 agonists in combination with TLR3, TLR4, and TLR9 agonists synergistically induce IL-12 and IFN-gamma production in DCs to induce Th1-lineage immune responses. ..
  9. Faustin B, Lartigue L, Bruey J, Luciano F, Sergienko E, Bailly Maitre B, et al. Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation. Mol Cell. 2007;25:713-24 pubmed
    ..The findings provide the biochemical basis for understanding how inflammasome assembly and function are regulated, and shed light on NALP1 as a direct sensor of bacterial components in host defense against pathogens. ..
  10. Mpofu C, Campbell B, Subramanian S, Marshall Clarke S, Hart C, Cross A, et al. Microbial mannan inhibits bacterial killing by macrophages: a possible pathogenic mechanism for Crohn's disease. Gastroenterology. 2007;133:1487-98 pubmed
    ..The inhibitory activity was removed by GNA-affinity chromatography. Suppression of mucosal phagocyte function by microbial mannans, possibly of Mycobacterial origin, may contribute to CD pathogenesis. ..
  11. Yang S, Tamai R, Akashi S, Takeuchi O, Akira S, Sugawara S, et al. Synergistic effect of muramyldipeptide with lipopolysaccharide or lipoteichoic acid to induce inflammatory cytokines in human monocytic cells in culture. Infect Immun. 2001;69:2045-53 pubmed
  12. Hedl M, Li J, Cho J, Abraham C. Chronic stimulation of Nod2 mediates tolerance to bacterial products. Proc Natl Acad Sci U S A. 2007;104:19440-5 pubmed
    ..Significantly, intestinal macrophages exhibit tolerance to MDP per production of inflammatory cytokines. These results illustrate a role for chronic stimulation of Nod2 in mediating tolerance to bacterial products. ..
  13. Watanabe T, Asano N, Murray P, Ozato K, Tailor P, Fuss I, et al. Muramyl dipeptide activation of nucleotide-binding oligomerization domain 2 protects mice from experimental colitis. J Clin Invest. 2008;118:545-59 pubmed publisher
  14. Hsu L, Ali S, McGillivray S, Tseng P, Mariathasan S, Humke E, et al. A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion in response to Bacillus anthracis infection and muramyl dipeptide. Proc Natl Acad Sci U S A. 2008;105:7803-8 pubmed publisher
    ..Thus, NOD2 plays a key role in the B. anthracis-induced inflammatory response by being a critical mediator of IL-1beta secretion. ..
  15. Maeda S, Hsu L, Liu H, Bankston L, Iimura M, Kagnoff M, et al. Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL-1beta processing. Science. 2005;307:734-8 pubmed
    ..These effects are linked to increased susceptibility to bacterial-induced intestinal inflammation and identify NOD2 as a positive regulator of NF-kappaB activation and IL-1beta secretion. ..
  16. Vavricka S, Musch M, Chang J, Nakagawa Y, Phanvijhitsiri K, Waypa T, et al. hPepT1 transports muramyl dipeptide, activating NF-kappaB and stimulating IL-8 secretion in human colonic Caco2/bbe cells. Gastroenterology. 2004;127:1401-9 pubmed
    ..Because hPepT1 expression in chronic colonic inflammation is increased, this may play an important role in promoting colonocyte participation in host defense and pathogen clearance through increased uptake of MDP. ..
  17. Kerns H, Jutila M, Hedges J. The distinct response of gammadelta T cells to the Nod2 agonist muramyl dipeptide. Cell Immunol. 2009;257:38-43 pubmed publisher
    ..The results indicate priming of gammadelta T cells by MDP, and offer definitive evidence of the expression of functional Nod2 in gammadelta T cells. ..
  18. Madu S, Faurie A, Pettifor J, Laburn H. Growth failure after recurrent fever in young guinea pigs. Physiol Behav. 2007;90:656-63 pubmed
  19. Mori K, Ando K, Heymann D. Liposomal muramyl tripeptide phosphatidyl ethanolamine: a safe and effective agent against osteosarcoma pulmonary metastases. Expert Rev Anticancer Ther. 2008;8:151-9 pubmed publisher
    ..Although surgery will remain the main approach for osteosarcoma treatment of lung metastases, L-MTP-PE combined with other modalities, including chemotherapy, appears to be of benefit in these patients as well. ..
  20. Piispanen A, Hogan D. PEPped up: induction of Candida albicans virulence by bacterial cell wall fragments. Cell Host Microbe. 2008;4:1-2 pubmed publisher
    ..Conserved elements in human and fungal detection of muramyl dipeptides highlight a common ability to perceive proximal bacterial populations. ..
  21. Wang T, Dabbas B, Laperriere D, Bitton A, Soualhine H, Tavera Mendoza L, et al. Direct and indirect induction by 1,25-dihydroxyvitamin D3 of the NOD2/CARD15-defensin beta2 innate immune pathway defective in Crohn disease. J Biol Chem. 2010;285:2227-31 pubmed publisher
  22. Dzierzbicka K, Trzonkowski P, Sewerynek P, Mysliwski A. Synthesis and cytotoxic activity of conjugates of muramyl and normuramyl dipeptides with batracylin derivatives. J Med Chem. 2003;46:978-86 pubmed
    ..During tests performed at Medical University of Gdansk, Poland, two analogues 11c and 11e reduced the proliferation of Ab melanoma cells in vitro compared with batracylin alone (Table 2, Figure 1). ..
  23. Brosbøl Ravnborg A, Hvas C, Agnholt J, Dahlerup J, Vind I, Till A, et al. Toll-like receptor-induced granulocyte-macrophage colony-stimulating factor secretion is impaired in Crohn's disease by nucleotide oligomerization domain 2-dependent and -independent pathways. Clin Exp Immunol. 2009;155:487-95 pubmed publisher
    ..The defect in GM-CSF secretion suggests a hitherto unknown role of NOD2 in the pathogenesis of CD and is consistent with the hypothesis that impaired GM-CSF secretion in part constitutes a NOD2-dependent disease risk factor. ..
  24. Dietz H, Pfeifle D, Wiedemann B. The signal molecule for beta-lactamase induction in Enterobacter cloacae is the anhydromuramyl-pentapeptide. Antimicrob Agents Chemother. 1997;41:2113-20 pubmed
    ..These findings indicate that aD-pentapeptide is the main periplasmic muropeptide, which is converted into the cytoplasmic signal molecule for beta-lactamase induction, the aM-pentapeptide. ..
  25. Su Y, Zhang Z, Trautmann K, Xu S, Schluesener H. TLR and NOD2 ligands induce cell proliferation in the rat intact spinal cord. J Neuropathol Exp Neurol. 2005;64:991-7 pubmed
    ..These findings suggest an intricate interaction of phylogenetically ancient cellular processes of the innate immune system and regeneration. ..
  26. Kiseleva E, Te E, Korostylev A. [Clinical laboratory substantiation of immunocorrection use in comprehensive treatment of chronic catarrhal gingivitis]. Stomatologiia (Mosk). 2007;86:34-7 pubmed
    ..The role of immune system in development of chronic catarrhal gingivitis in 60 primary patients was defined and substantition of immunocorrection with Licopid in combined treatment was done. ..
  27. Kosovac K, Brenmoehl J, Holler E, Falk W, Schoelmerich J, Hausmann M, et al. Association of the NOD2 genotype with bacterial translocation via altered cell-cell contacts in Crohn's disease patients. Inflamm Bowel Dis. 2010;16:1311-21 pubmed publisher
  28. Werner G. Natural and synthetic peptides (other than neuropeptides) endowed with immunomodulating activities. Immunol Lett. 1987;16:363-70 pubmed
  29. Johansson J, Ledin A, Vernersson M, Lovgren Bengtsson K, Hellman L. Identification of adjuvants that enhance the therapeutic antibody response to host IgE. Vaccine. 2004;22:2873-80 pubmed
    ..Hence, adjuvants based on pure mineral oil without additional immuno-stimulatory substances appear to be the best adjuvant candidates in therapeutic vaccines aimed at regulating the in vivo levels of self-proteins. ..
  30. Cooney R, Baker J, Brain O, Danis B, Pichulik T, Allan P, et al. NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat Med. 2010;16:90-7 pubmed publisher
  31. Funayama H, Huang L, Asada Y, Endo Y, Takada H. Enhanced induction of a histamine-forming enzyme, histidine decarboxylase, in mice primed with NOD1 or NOD2 ligand in response to various Toll-like receptor agonists. Innate Immun. 2010;16:265-72 pubmed publisher
    ..These findings suggest that HDC is induced in association with TLRs and NOD1/2, and that the newly formed histamine by the induced HDC might play important roles in the regulation of inflammatory and immune responses in various organs. ..
  32. Bertrand M, Doiron K, Labbe K, Korneluk R, Barker P, Saleh M. Cellular inhibitors of apoptosis cIAP1 and cIAP2 are required for innate immunity signaling by the pattern recognition receptors NOD1 and NOD2. Immunity. 2009;30:789-801 pubmed publisher
    ..This discovery provides therapeutic opportunities in the treatment of NOD-dependent immunologic and inflammatory diseases. ..
  33. Marks D, Radulovic M, McCartney S, Bloom S, Segal A. Modified skin window technique for the extended characterisation of acute inflammation in humans. Inflamm Res. 2007;56:168-74 pubmed
    ..The modifications enable broad characterisation of inflammatory responses and administration of exogenous immunomodulators. ..
  34. Muhvic D, El Samalouti V, Flad H, Radosevic Stasic B, Rukavina D. The involvement of CD14 in the activation of human monocytes by peptidoglycan monomers. Mediators Inflamm. 2001;10:155-62 pubmed
    ..Activation of human monocytes by PGM involves both forms of CD14 molecule, sCD14 and mCD14. ..
  35. Iwasaki T, Kaneko N, Ito Y, Takeda H, Sawasaki T, Heike T, et al. Nod2-Nodosome in a Cell-Free System: Implications in Pathogenesis and Drug Discovery for Blau Syndrome and Early-Onset Sarcoidosis. ScientificWorldJournal. 2016;2016:2597376 pubmed publisher
    ..Thus, we successfully developed Nod2-nodosome in a cell-free system reflecting its function in vivo, and it can be useful for screening Nod2-nodosome-targeted therapeutic molecules for BS/EOS and granulomatous inflammatory diseases. ..
  36. Pertel S, Kadun A, Kakaian E, Chirva V, Krivorutchenko I, Krivoshein I, et al. [Synthesis and biological activity of anomeric muramoyldipeptide butylglycosides]. Bioorg Khim. 1999;25:708-15 pubmed
    ..The biological activity of anomeric muramyl dipeptides was shown to depend essentially on the configuration of their anomeric center. ..
  37. Nelson E, Wong Y, Yu L, Fok T, Li K. Effects of hyperthermia and muramyl dipeptide on IL-1beta, IL-6, and mortality in a neonatal rat model. Pediatr Res. 2002;52:886-91 pubmed
    ..66 (1.20-5.92)]. We conclude that hyperthermia and a surrogate of infection (MDP) influence cytokine production and that the combination of heat stress and MDP increases mortality in the neonatal rat. ..
  38. Anderson P, Tomaras M, McConnell K. Mifamurtide in osteosarcoma--a practical review. Drugs Today (Barc). 2010;46:327-37 pubmed publisher
  39. Yamashita T, Takahashi N, Yang S, Sato N, Udagawa N. [Bone destruction caused by osteoclasts]. Clin Calcium. 2006;16:234-40 pubmed
    ..TLR4 and NOD2 recognize bacterial components on cell surfaces and inside cells, respectively, and these signals up-regulate RANKL expression in osteoblasts, which results in enhancing osteoclast formation and function. ..
  40. Nikitin A, Abidov M, Kovalevskaya E, Kalyuzhin O. Search for potent modulators of cytokine production by macrophages. Bull Exp Biol Med. 2004;138:259-61 pubmed
    ..Licopid produced a costimulatory effect on macrophages primed with endotoxin. Tamerit in different doses suppressed cytokine production by cells. Polyoxidony in low doses activated, but in high doses suppressed this process. ..
  41. Goasduff T, Darcissac E, Vidal V, Capron A, Bahr G. The transcriptional response of human macrophages to murabutide reflects a spectrum of biological effects for the synthetic immunomodulator. Clin Exp Immunol. 2002;128:474-82 pubmed
  42. Sevcik J, Masek K. The interaction of immunomodulatory muramyl dipeptide with peripheral 5-HT receptors: overview of the current state. Int J Immunopharmacol. 1999;21:227-32 pubmed
    ..Since new 5-HT receptor types have emerged recently, new studies are under way. The results might contribute to the development of novel immunomodulatory drugs devoid of adverse effects. ..
  43. Sharma P, Singh N, Garg R, Haq W, Dube A. Efficacy of human beta-casein fragment (54-59) and its synthetic analogue compound 89/215 against Leishmania donovani in hamsters. Peptides. 2004;25:1873-81 pubmed
    ..001). This peptide also exhibited considerably good therapeutic efficacy when evaluated either alone or in combination with SAG in established infection of L. donovani. ..
  44. Mrakovcic Sutic I, Radosević Stasić B, Simin M, Muhvic D, Rukavina D. Augmentation of NKT and NK cell-mediated cytotoxicity by peptidoglycan monomer linked with zinc. Mediators Inflamm. 2002;11:129-35 pubmed
    ..Destruction of thymocytes increased by 10 and 50%, respectively. The results point to PGM-Zn as a potent cytotoxicity-inducing agent, which also generates autoreactive NKT cells. ..
  45. Charriere G, Ip W, Dejardin S, Boyer L, Sokolovska A, Cappillino M, et al. Identification of Drosophila Yin and PEPT2 as evolutionarily conserved phagosome-associated muramyl dipeptide transporters. J Biol Chem. 2010;285:20147-54 pubmed publisher
  46. Netea M, Azam T, Ferwerda G, Girardin S, Walsh M, Park J, et al. IL-32 synergizes with nucleotide oligomerization domain (NOD) 1 and NOD2 ligands for IL-1beta and IL-6 production through a caspase 1-dependent mechanism. Proc Natl Acad Sci U S A. 2005;102:16309-14 pubmed
    ..The modulation of intracellular NOD2 pathways by IL-32, but not cell-surface TLRs, and the marked expression of IL-32 in colon mucosa suggest a role of IL-32 in the pathogenesis of Crohn's disease. ..
  47. Deng L, Humphries D, Arbeit R, Carlton L, Smole S, Carroll J. Identification of a novel peptidoglycan hydrolase CwlM in Mycobacterium tuberculosis. Biochim Biophys Acta. 2005;1747:57-66 pubmed
    ..tuberculosis. CwlM offers a new target for a unique class of drugs that could alter the permeability of the mycobacterial cell wall and enhance the effectiveness of treatments for tuberculosis. ..
  48. Fehér K, Pristovsek P, Szilagyi L, Ljevaković D, Tomasić J. Modified glycopeptides related to cell wall peptidoglycan: conformational studies by NMR and molecular modelling. Bioorg Med Chem. 2003;11:3133-40 pubmed
  49. Hitotsumatsu O, Ahmad R, Tavares R, Wang M, Philpott D, Turer E, et al. The ubiquitin-editing enzyme A20 restricts nucleotide-binding oligomerization domain containing 2-triggered signals. Immunity. 2008;28:381-90 pubmed publisher
    ..These findings indicate that A20 directly restricts NOD2 induced signals in vitro and in vivo, and provide new insights into how these signals are physiologically restricted. ..
  50. van Heel D, Hunt K, Ghosh S, Hervé M, Playford R. Normal responses to specific NOD1-activating peptidoglycan agonists in the presence of the NOD2 frameshift and other mutations in Crohn's disease. Eur J Immunol. 2006;36:1629-35 pubmed
    ..Responses to specific NOD1 agonists are unaffected by NOD2 genotype, suggesting independent action of the NOD1 and NOD2 pathways. ..
  51. Ferwerda G, Kramer M, de Jong D, Piccini A, Joosten L, Devesaginer I, et al. Engagement of NOD2 has a dual effect on proIL-1beta mRNA transcription and secretion of bioactive IL-1beta. Eur J Immunol. 2008;38:184-91 pubmed
    ..This demonstrates that both caspase-1-dependent and -independent mechanisms are involved in the synergy between NOD2 and TLR. ..
  52. Kim Y, Park J, Daignault S, Fukase K, Nunez G. Cross-tolerization between Nod1 and Nod2 signaling results in reduced refractoriness to bacterial infection in Nod2-deficient macrophages. J Immunol. 2008;181:4340-6 pubmed
    ..These results demonstrate that cross-tolerization between Nod1 and Nod2 leads to increase recognition of both pathogenic and commensal bacteria in Nod2-deficient macrophages pre-exposed to microbial ligands...
  53. Gobec S, Urleb U, Auger G, Blanot D. Synthesis and biochemical evaluation of some novel N-acyl phosphono- and phosphinoalanine derivatives as potential inhibitors of the D-glutamic acid-adding enzyme. Pharmazie. 2001;56:295-7 pubmed
  54. Kamerman P, Fuller A. Effects of nitric oxide synthase inhibitors on the febrile response to lipopolysaccharide and muramyl dipeptide in guinea pigs. Life Sci. 2000;67:2639-45 pubmed
  55. Koutsos E, Klasing K. The acute phase response in Japanese quail (Coturnix coturnix japonica). Comp Biochem Physiol C Toxicol Pharmacol. 2001;128:255-63 pubmed
    ..001), while MDP had no effect. These data indicate that Japanese quail are less sensitive to MDP than LPS, and that quail demonstrate tolerance to LPS following repeated injections. ..
  56. von Meyenburg C, Hrupka B, Arsenijevic D, Schwartz G, Landmann R, Langhans W. Role for CD14, TLR2, and TLR4 in bacterial product-induced anorexia. Am J Physiol Regul Integr Comp Physiol. 2004;287:R298-305 pubmed
    ..The results are consistent with the hypothesis that TLR4 functions as the true LPS receptor and that TLR2 is involved in recognition of gram-positive bacterial products. ..
  57. Dzierzbicka K, Kołodziejczyk A, Wysocka Skrzela B, Mysliwski A, Sosnowska D. Synthesis and antitumor activity of conjugates of muramyldipeptide, normuramyldipeptide, and desmuramylpeptides with acridine/acridone derivatives. J Med Chem. 2001;44:3606-15 pubmed
    ..Analogues 4b and 4h were active in the in vivo hollow fiber assay (Table 5). Analogue 3a shows an immunostimulating effect on the cytotoxic activity of the NK cells obtained from the spleen of healthy and Ab melanoma bearing animals. ..
  58. Cottagnoud P, Gerber C, Majcherczyk P, Acosta F, Cottagnoud M, Neftel K, et al. The stereochemistry of the amino acid side chain influences the inflammatory potential of muramyl dipeptide in experimental meningitis. Infect Immun. 2003;71:3663-6 pubmed
    ..These data show that the inflammatory potential of MDPs depends on the stereochemistry of the first amino acid of the peptide side chain and suggest that intact pneumococci and MDPs induce inflammation by different pathways. ..
  59. Shah I, Laaberki M, Popham D, Dworkin J. A eukaryotic-like Ser/Thr kinase signals bacteria to exit dormancy in response to peptidoglycan fragments. Cell. 2008;135:486-96 pubmed publisher
    ..Thus, in contrast to traditional antimicrobials that inhibit metabolically active cells, staurosporine acts by blocking germination of dormant spores. ..
  60. Frkanec R, Noethig Laslo V, Vranesić B, Mirosavljević K, Tomasić J. A spin labelling study of immunomodulating peptidoglycan monomer and adamantyltripeptides entrapped into liposomes. Biochim Biophys Acta. 2003;1611:187-96 pubmed
    ..The study of possible interaction with liposomal membrane is relevant to the use of tested compounds incorporated into liposomes, as adjuvants in vivo. ..
  61. Meyers P, Schwartz C, Krailo M, Kleinerman E, Betcher D, Bernstein M, et al. Osteosarcoma: a randomized, prospective trial of the addition of ifosfamide and/or muramyl tripeptide to cisplatin, doxorubicin, and high-dose methotrexate. J Clin Oncol. 2005;23:2004-11 pubmed
    ..The addition of MTP to chemotherapy might improve EFS, but additional clinical and laboratory investigation will be necessary to explain the interaction between ifosfamide and MTP. ..
  62. Kinsner A, Pilotto V, Deininger S, Brown G, Coecke S, Hartung T, et al. Inflammatory neurodegeneration induced by lipoteichoic acid from Staphylococcus aureus is mediated by glia activation, nitrosative and oxidative stress, and caspase activation. J Neurochem. 2005;95:1132-43 pubmed
  63. Porter M, Hrupka B, Altreuther G, Arnold M, Langhans W. Inhibition of TNF-alpha production contributes to the attenuation of LPS-induced hypophagia by pentoxifylline. Am J Physiol Regul Integr Comp Physiol. 2000;279:R2113-20 pubmed
    ..This is consistent with the hypothesis that TNF-alpha plays a major role in the anorexia associated with bacterial infection...
  64. Zhan Y, Xu Y, Seah S, Brady J, Carrington E, Cheers C, et al. Resident and monocyte-derived dendritic cells become dominant IL-12 producers under different conditions and signaling pathways. J Immunol. 2010;185:2125-33 pubmed publisher
    ..In contrast, for mDC, IL-12 production was mainly dependent on MyD88 signaling. Thus, conventional DCs and mDCs use different pathways to regulate IL-12 production. ..
  65. Vidal V, Dewulf J, Bahr G. Enhanced maturation and functional capacity of monocyte-derived immature dendritic cells by the synthetic immunomodulator Murabutide. Immunology. 2001;103:479-87 pubmed
    ..As this immunomodulator is approved for administration in humans, it could be a useful adjunct to boost the efficacy of DC-based vaccines designed against tumours or virus-infected cells. ..
  66. van Beelen A, Zelinkova Z, Taanman Kueter E, Muller F, Hommes D, Zaat S, et al. Stimulation of the intracellular bacterial sensor NOD2 programs dendritic cells to promote interleukin-17 production in human memory T cells. Immunity. 2007;27:660-9 pubmed
    ..Thus, antibacterial Th17-mediated immunity in humans is orchestrated by DCs upon sensing bacterial NOD2-ligand MDP. ..
  67. Worth L, Jeha S, Kleinerman E. Biologic response modifiers in pediatric cancer. Hematol Oncol Clin North Am. 2001;15:723-40, ix pubmed
    ..The challenge is to incorporate biologic response modifiers into the treatment armamentarium in ways that will maximize their tumorigenicity. ..
  68. Fosset S, Fromentin G, Rampin O, Lang V, Mathieu F, Tome D. Pharmacokinetics and feeding responses to muramyl dipeptide in rats. Physiol Behav. 2003;79:173-82 pubmed
    ..Our data suggest that the hypophagic effect of MDP may result from satiety and sickness behavior. ..
  69. Frampton J. Mifamurtide: a review of its use in the treatment of osteosarcoma. Paediatr Drugs. 2010;12:141-53 pubmed publisher
    ..Based on the available data, mifamurtide can be considered for inclusion in treatment protocols for localized osteosarcoma. ..
  70. Odean M, Frane C, Van derVieren M, Tomai M, Johnson A. Involvement of gamma interferon in antibody enhancement by adjuvants. Infect Immun. 1990;58:427-32 pubmed
    ..It was concluded that the enhancement induced by the adjuvants LPS, poly(A)-poly(U), and murabutide is mediated in part by their action on T cells resulting in release of IFN-gamma suggesting activation of a common transmembrane signal. ..
  71. Tigno Aranjuez J, Asara J, Abbott D. Inhibition of RIP2's tyrosine kinase activity limits NOD2-driven cytokine responses. Genes Dev. 2010;24:2666-77 pubmed publisher
  72. Sridevi K, Neena K, Chitralekha K, Arif A, Tomar D, Rao D. Expression of costimulatory molecules (CD80, CD86, CD28, CD152), accessory molecules (TCR alphabeta, TCR gammadelta) and T cell lineage molecules (CD4+, CD8+) in PBMC of leprosy patients using Mycobacterium leprae antigen (MLCWA) with murabutide and . Int Immunopharmacol. 2004;4:1-14 pubmed
    ..The study highlights the reversal of T cell anergy especially in lepromatous patients through the modulation of costimulatory molecule expression under the influence of Th1 cytokines, i.e., IL-2 and IFNgamma. ..
  73. Plata Salaman C. 1998 Curt P. Richter Award. Brain mechanisms in cytokine-induced anorexia. Psychoneuroendocrinology. 1999;24:25-41 pubmed
  74. Zemliakov A, Tsikalov V, Kaliuzhin O, Kur ianov V, Chirva V. [N-acetylmuramyl-L-alanyl-D-isoglutamine glycosides. Effect of glycoside center configuration and aglycone nature on biological activity]. Bioorg Khim. 2003;29:316-22 pubmed
    ..In the case of alkyl beta-glycosides, differences in hydrocarbon chain lengths (C4-C8) and in aglycone (aliphatic chain and aliphatic or aromatic ring) exerted no substantial effect on the immunostimulating activity. ..
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