Distinctive immunomodulating properties and interactivity with model membranes and cells of two homologous muramyl dipeptide derivatives differing by their lipophilicity

Kalyuzhin, O. V.; Zemlyakov, A. E.; Fuchs, Boris

doi:10.1016/s0192-0561(96)00061-6

Cited by 12 publications

(16 citation statements)

References 19 publications

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“…Our findings confirm previous data that glymuride modifies T-and B-cell immunity in vitro [3,7]. Immunomodulating drugs are now widely used in therapy of many diseases, notably improving the treatment efficiency [6].…”

Section: Resultssupporting

confidence: 90%

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In vitro immunomodulating activity of β-heptylglycoside muramyldipeptide

et al. 1999

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The effects of [3-heptylglycoside muramyldipeptide (glymuride) on antibody production and delayed type hypersensitivity reaction were studied in mice with weak and strong reactions to sheep erythrocytes. The drug exhibited high immunomodulating activity which depended on the initial genetically determined immunoreactivity of animals and drug dose. Key Words: ~-heptylglycoside muramyldipeptide; antibody production; delayed type hypersensitivityImmunomodulators modifying the direction and intensity of immune reactions occupy a special place among modern immunotropic drugs. The type of biological effect (stimulation or suppression) is determined by a sum of factors: drug dose, number of administrations, initial immunity status, etc.We investigated the dose-dependent effects of [~-heptylglycoside muramyldipeptide (glymuride) on immunoreactivity of mice with genetically predetermined strong and weak reaction to sheep erythrocytes (SE). MATERIALS AND METHODSExperiments were performed on 6-8-week-old CBA and C57B1/6 mice (Kryukovo Breeding Center, Russian Academy of Medical Sciences), [3-Heptylglycoside-N-acetylmuramyl-L-alanyl-D-isoglutamine (glymuride) was synthesized as described previously [1]. The effect of glymuride on delayed type hypersensitivity (DTH) reaction was studied by a previously described method [4]. The effect on the production of antibodies to SE was evaluated as described elsewhere [5]. Glymuride was injected intravenously in doses of 0.2, 20, and 200 gg/mouse in 100 gl normal saline. Control mice were intravenously injected with 100 ~tl normal saline. RESULTSIn in vitro test systems [3-heptylglycoside-muramyldipeptide activated T-and B-cell immunity [2,3,7]. It stimulated lymphocyte proliferation in response to Tand B-cell mitogens and activated the generation of allospecific cytotoxic T lymphocytes in a mixed lymphocyte culture. We investigated the effect of glymuride on cell and humoral immunity in vivo. The effect on humoral immunity was evaluated by the intensity of the production of antibodies (agglutinins) to SE in mice of two oppositely reacting strains, CBA and C57B1/6, injected with glymuride (Table 1). On day 4, anti-SE antibody titer increased in all mice. On days 4-7, serum concentrations of antibodies in CBA mice (strongly reacting) treated with glymuride were virtually the same as in the control. On day 14, antibody titers were lower than in controls. However, increased level of antibodies persisted up to day 21 of the experiment, while in CBA mice immunized with SE alone antibody titers dropped at this period.In weakly reacting C57BL/6 mice a statistically significant (p<0.05) increase in agglutinin concentration was observed in groups injected with glymuride in doses of 200 (days 4 and 21) and 20 ~tg/mouse (day 7).

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Section: Resultssupporting

confidence: 90%

“…In in vitro test systems [3-heptylglycoside-muramyldipeptide activated T-and B-cell immunity [2,3,7]. It stimulated lymphocyte proliferation in response to Tand B-cell mitogens and activated the generation of allospecific cytotoxic T lymphocytes in a mixed lymphocyte culture.…”

Section: Resultsmentioning

confidence: 99%

In vitro immunomodulating activity of β-heptylglycoside muramyldipeptide

et al. 1999

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“…These findings and the results of previous studies of the immunomodulating effect of glymuride in vitro [4,5,7] indicate that glymuride is a promising agent for clinical use. Its high efficacy upon oral and intravenous administration extends the probane torms of its application.…”

Section: Methodssupporting

confidence: 68%

“…From these results, EDso calculated for oral and tor intravenous administration were 0.75_+0.1 and 0.2 mg/kg, respectively. Presumably, the immunomodulating activity of glymuride in vivo and good assimilation after oral intake are largely due to its effective penetration through biological membranes, which is explained by a combination of hydro-and lipophilic properties in the glymuride molecule [4,7].…”

Section: Methodsmentioning

confidence: 99%

“…Several MDP analogs are now clinically tried, some including a Russian-made drug licopide, are used in clinical practice [3,6]. A perspective original muramyl peptide [3-heptylglycoside MDP (glymuride) stimulates the main components of the antitumor and antiinfectious immunity in model test systems in vitro [4,5,7]. Its effect is superior to that of non-modified MDP and its derivatives.…”

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confidence: 99%

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Stimulation of nonspecific resistance in mice by β-heptylglycoside muramyl dipeptide

Kalyuzhin

Zemlyakov

et al. 1999

Bull Exp Biol Med

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The ability of 13-heptylglycoside muramyl dipeptide (glymuride) to stimulme nonspecific resistance in mice is studied. Glymuride prevents the death of up to 80% animals intraperitoneally infected with Salmonella typhi in a dose of 100 LD~ 0. Glymuride is effective in both oral and intravenous administration. The EDs0 for these routes of administration are calculated. Key Words: [5-heptylglycoside muramyl dipeptide; Salmonella typhi; nonspec(f~c resistanceSearch for new effective synthetic derivatives of bacterial muramyl dipeptide (MDP) has been in progress tor more than two decades. Several MDP analogs are now clinically tried, some including a Russian-made drug licopide, are used in clinical practice [3,6]. A perspective original muramyl peptide [3-heptylglycoside MDP (glymuride) stimulates the main components of the antitumor and antiinfectious immunity in model test systems in vitro [4,5,7]. Its effect is superior to that of non-modified MDP and its derivatives.We investigated the capacity of this drug to stimulate nonspecific antiinfectious immunity and prevent animal death caused by intraperitoneal Salmonella typhi infection and determined the EDs0 for oral and intravenous administration of glymuride.

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Biological activity of anomeric pairs of lipophilic glycosides of N-acetylmuramyl-L-alanyl-D-isoglutamine

et al. 2008

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We studied the capacity of anomeric pairs of alpha- and beta-dodecyl, alpha- and beta-(1-pentylhexyl), and alpha- and beta-cyclododecyl glycosides of N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide) to stimulate the nonspecific resistance of mice to intraperitoneal infection of Staphylococcus aureus and Escherichia coli cultures. Intraperitoneal pretreatment with the test substances in a wide dose range increased survival of infected animals. No differences were found between the biological effects of alpha- and beta-dodecyl and alpha- and beta-(1-pentylhexyl) glycosides of muramyl dipeptide. An inverse relationship was found between stimulatory activity and dose of alpha- and beta-cyclododecyl glycosides of muramyl dipeptide during sepsis caused by Staphylococcus aureus.

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Distinctive immunomodulating properties and interactivity with model membranes and cells of two homologous muramyl dipeptide derivatives differing by their lipophilicity

Cited by 12 publications

References 19 publications

In vitro immunomodulating activity of β-heptylglycoside muramyldipeptide

In vitro immunomodulating activity of β-heptylglycoside muramyldipeptide

Stimulation of nonspecific resistance in mice by β-heptylglycoside muramyl dipeptide

Biological activity of anomeric pairs of lipophilic glycosides of N-acetylmuramyl-L-alanyl-D-isoglutamine

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