Disease relevance of N-Acetylmuramyl-L-alanyl-D-isoglutamine

• Adjuvant polyarthritis. V. Induction by N-acetylmuramyl-L-alanyl-D-isoglutamine, the smallest peptide subunit of bacterial peptidoglycan [1].
• Enhancement of nonspecific immunity to Klebsiella pneumoniae infection by a synthetic immunoadjuvant (N-acetylmuramyl-L-alanyl-D-isoglutamine) and several analogs [2].
• A synthetic water soluble adjuvant (N-acetyl-muramyl-L-alanyl-D-isoglutamine) was also shown to potentiate the immune response of hamsters to A/NJ/76 [Hswl NI] influenza virus subunit vaccines [3].
• Intracutaneous injection of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) in guinea pigs caused an extensive necrotic reaction in footpads prepared by injection of heat-killed Mycobacterium tuberculosis in water-in-mineral-oil emulsion [4].
• The antitumor activity of a mixture of synthetic N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and trehalose-6,6'-dimycolate (TDM) (MDP+TDM) in emulsified form was studied in guinea pigs, each with a syngeneic dermal tumor and microscopically detectable metastases in regional lymph nodes [5].

Psychiatry related information on N-Acetylmuramyl-L-alanyl-D-isoglutamine

• The synthetic muramyl dipeptide, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), is reported to increase slow-wave sleep and body temperature in cats, rabbits, and squirrel monkeys [6].
• Treatment of cultured monocytes with the synthetic adjuvants N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and its lipophilic derivative, [B30]-MDP, did not significantly affect the D2V permissiveness of the cells [7].
• The effect of intravenous administration of a nonpyrogenic (25 micrograms/kg) and pyrogenic (2000 micrograms/kg) dose of N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP) on sleep stages was tested [8].

High impact information on N-Acetylmuramyl-L-alanyl-D-isoglutamine

• Data presented here demonstrate that the resulting immunological castration can be obtained by administering in an aqueous medium the synthetic decapeptide directly conjugated to the synthetic immunomodulator glycopeptide N-acetylmuramyl-L-alanyl-D-isoglutamine [9].
• N-Acetylmuramyl-L-alanyl-D-isoglutamine was capable of inducing Kupffer cell tumoricidal activity in vitro: its failure to induce tumoricidal activity in situ at doses of 1,000 micrograms demonstrates the utility of liposomal carriers for the in vivo activation of Kupffer cells by muramyl dipeptides [10].
• Calreticulin (CRT) is a binding protein for apoptotic N-acetylmuramyl-L-alanyl-D-isoglutamine (L,D-MDP) or peptidoglycan in RK(13) cells [11].
• A synthetic muramyl dipeptide (MDP, N-acetylmuramyl-L-alanyl-D-isoglutamine) is a minimal essential structure that is contained generally in bacterial cell walls and is responsible for their many biologic activities such as adjuvant activity, pyrogenicity, and a capacity to confer resistance against bacterial and viral infections [12].
• Native collagen (type II) from human costal cartilage was emulsified with incomplete Freund's adjuvant (IFA) containing the synthetic adjuvant N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), and injected into one hind footpad of the PVG/c rat [13].

Chemical compound and disease context of N-Acetylmuramyl-L-alanyl-D-isoglutamine

• A synthetic muramyl dipeptide, N-acetylmuramyl-L-alanyl-D-isoglutamine, dissolved in saline only and applied subcutaneously to rats of the Lewis inbred strain, produced arthritis, clinically manifest by hind feet paresis but without apparent paw swelling in most cases [14].
• Adjuvant-active murabutide (N-acetylmuramyl-L-alanyl-D-glutamine-alpha-n-butyl ester), devoid of the side effects of muramyl dipeptide (N-acetylmuramyl-L-alanyl-D-isoglutamine), was administered in saline with natural and synthetic hepatitis B surface antigens (HBsAgs) [15].
• Adjuvant activity of carbohydrate analogs of N-acetylmuramyl-L-alanyl-D-isoglutamine on the induction of delayed-type hypersensitivity to azobenzenearsonate-N-acetyl-L-tyrosine in guinea pigs [16].
• Furthermore, two cell wall compounds from Mycobacterium tuberculosis, trehalose 6,6'-dimycolate and N-acetylmuramyl-L-alanyl-D-isoglutamine, which are active components of Freund's adjuvant, were used [17].
• Immunostimulants like levamisole, BCG, a protein polysaccharide from myceria Coriolus vesicolor PS-K, a streptoccocal preparation OK-432 and immunomodulators like N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and its analogs [18].

Biological context of N-Acetylmuramyl-L-alanyl-D-isoglutamine

• A synthetic adjuvant, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), was previously shown to enhance polyclonal antibody response in murine spleen cell cultures [19].
• Possible chemotaxis of human monocytes by N-acetylmuramyl-L-alanyl-D-isoglutamine [20].
• Kinetics of the humoral and cellular immune response of guinea pigs after injection of the synthetic adjuvant N-acetylmuramyl L-alanyl-D-isoglutamine: comparison with Freund complete adjuvant [21].
• Immunization of mice with three or four doses (10 micrograms each) of f-TXD and the synthetic adjuvant N-acetylmuramyl-L-alanyl-D-isoglutamine (50 micrograms) induced high levels of antiexotoxin A antibodies as measured by passive hemagglutination assay and enzyme-linked immunosorbent assay [22].
• In these studies, SAA synthesis has been used as an index of macrophage activation to examine the in vivo response of mice to challenge with seven different mycobacteria and with synthetic analogs of the immunoadjuvant N-acetylmuramyl-L-alanyl-D-isoglutamine [MDP(L-D)] [23].

Anatomical context of N-Acetylmuramyl-L-alanyl-D-isoglutamine

• The adjuvant effects of mycobacteria can be replaced by more chemically defined isolates of the cell walls including a water soluble fraction (WSA) and by the synthetic analog N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP), which is the minimal structure required for adjuvanticity [24].
• Enhancement of carrier-specific helper T cell function by the synthetic adjuvant, N-acetyl muramyl-L-alanyl-D-isoglutamine (MDP) [25].
• It has been previously reported that N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP), which represents the minimal structure that can substitute for mycobacteria in Freund complete adjuvant, activated macrophages in vitro and in vivo [26].
• The influence of N-acetyl-muramyl-L-alanyl-D-isoglutamine (muramyl dipeptide, MDP) on the plaque-forming cell (PFC) response of mice to sheep red blood cells (SRBC) was studied [27].
• It was finally revealed that guinea pig ileum strips showed a definite contractile response to N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and 6-O-stearoyl- and 6-O-(2-tetradecylhexadecanoyl)-MDPs, but not to their analogs, whose C-terminal amino acid was L-isoglutamine or D-isoasparagine in place of D-isoglutamine and which lacked adjuvancy [28].

Associations of N-Acetylmuramyl-L-alanyl-D-isoglutamine with other chemical compounds

• Synthetic molecules (muramyl dipeptides), such as N-acetylmuramyl-L-alanyl-D-isoglutamine or murabutide, known as macrophage activators, are also efficient in revealing the cytokine hyperexpression in sg/sg macrophages [29].
• Macrophages from A/J mice have impaired responses in vitro to macrophage activating factor, gamma-interferon, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) or lipopolysaccharide when compared with macrophages from normoresponsive C57BL/6J mice [30].
• 3. The production of the neurotrophic supernatant was dose-dependent on myelin fraction and specific for myelin because supernatants from macrophages incubated with LPS (lipoplysaccharide), MDP (N-acetylmuramyl-L-alanyl-D-isoglutamine) or latex beads were not neurotrophic [31].
• The effect of methyl esterification of the isoglutamine residue in 6-O-acylated muramyl dipeptide (MDP) on some biological activities was investigated [32].
• Another soluble agent, N-acetylmuramyl-L-alanyl-D-isoglutamine, or phagocytable agents, silica and zymosan, also stimulated IL-1 production by Kupffer cells, whereas phorbol myristate acetate did not [33].

Gene context of N-Acetylmuramyl-L-alanyl-D-isoglutamine

• If this hypothesis is correct, then inhibition of endogenous IL-1 should reduce both normal sleep and N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP)-induced sleep [34].
• Also IL-4 and IFN-gamma are released by PA in quantities higher than those induced by TA and MDP [35].
• At concentration of 10 micrograms/ml; PA induces roughly +180% release of TNF with respect to controls, while release of IL-1 alpha is about 500% control values, and is higher than those obtained when cells are treated with TA and MDP; IL-6 release is higher than that stimulated by Con A, used as standard challenge [35].
• Two muramyl dipeptides, N-acetylmuramyl-L-alanyl-D-isoglutamine and its adjuvant-inactive isomer N-acetylmuramyl-D-alanyl-D-isoglutamine, were examined for their ability to protect mice carrying the CBA/N immune deficiency gene (xid) against lethal bacterial challenge [36].
• Muramyl dipeptide (MDP) and Escherichia coli LPS also stimulated TNF-alpha and IL-6 mRNA expression [37].

Analytical, diagnostic and therapeutic context of N-Acetylmuramyl-L-alanyl-D-isoglutamine

• Muramyl dipeptide, N-acetylmuramyl-L-alanyl-D-isoglutamine, induced adjuvant arthritis in WKA rats when injected in a water-in-oil emulsion prepared with Freund incomplete adjuvant (Difco), but not when emulsified with Drackeol and Arlacel A [38].
• N-acetylmuramyl-L-alanyl-D-isoglutamine stimulates the immune response of B cells. Use of fast protein liquid chromatography to purify a novel monokine involved in this effect [39].
• On the other hand, oral administration of muramyl dipeptide (MDP) with antigen boosted anti-TNP responses in C3H/HeN, but not in C3H/HeJ, mice [40].
• A synthetic analogue to those substances, muramyl dipeptide (MDP, N-acetylmuramyl-L-alanyl-D-isoglutamine), was found to induce prolonged increases in slow-wave sleep and to increase electroencephalographic (EEG) delta-wave activity [41].

References