Evidence for correlation between the intensities of adjuvant effects and NOD2 activation by monomeric, dimeric and lipophylic derivatives of N-acetylglucosaminyl-N-acetylmuramyl peptides

Selection of Adjuvants for Enhanced Vaccine Potency

“…A series of di, tetrasaccharide peptides and their stearoyl derivatives were found to activate NF-kB pathway through NOD2 [404]. While muramyl peptides preferentially stimulate IgG1 production, the tetrasaccharide containing muramyl peptide induces additional production of IgG2b subclasses [404].…”

“…A series of di, tetrasaccharide peptides and their stearoyl derivatives were found to activate NF-kB pathway through NOD2 [404]. While muramyl peptides preferentially stimulate IgG1 production, the tetrasaccharide containing muramyl peptide induces additional production of IgG2b subclasses [404]. However, muramyl dipeptide (MDP), a component of the peptidoglycan polymer, has minimal adjuvant properties for antibody production compared to the TLR agonist lipopolysaccharide under a variety of immunization conditions [401].…”

Muropeptides trigger distinct activation profiles in macrophages and dendritic cells

“…All above-mentioned GM-and Lac-peptides contained meso-DAP and were presumably recognized by NOD1. To investigate whether a NOD2 agonist would differentially affect DCs and Mphi as well, cells were stimulated with a NOD2 ligand, GM-2P [10]. Again, only Mphi made TNF-α, whereas DCs did not respond (Fig.…”

“…Most potent NOD1 agonists are Nacetylmuramyl tripeptide MurNAc-L-Ala-D-isoGln-meso-DAP and the corresponding N-acetylglucosaminyl N-acetylmuramyl tripeptide GlcNAc-MurNAc-L-Ala-D-isoGln-meso-DAP (GM-3P), followed by the tripeptide L-Ala-D-isoGln-meso-DAP, dipeptide D-isoGln-meso-DAP and lactoyl tripeptide Lac-L-Ala-D-isoGln-meso-DAP (Lac-3P) [4,9]. NOD2 detects N-acetylmuramyl dipeptide MurNAc-L-Ala-DisoGln and N-acetylglucosaminyl N-acetylmuramyl dipeptide GlcNAcMurNAc-L-Ala-D-isoGln (GM-2P), which are structural components of PG from both Gram-negative and Gram-positive bacteria; in addition, NOD2 senses muramyl tripeptides with terminal L-lysine [3,9,10].…”

Clinical and Immunological Efficiency of Muramyl Dipeptide in the Treatment of Atopic Diseases

“…В этом отношении наиболее перспективными «поляризаторами» иммунного ответа в настоящее время являются агонисты рецепторов врожден-ного иммунитета: синтетические и природные минимальные биологически активные фрагмен-ты (МБАФ) патоген-ассоциированных молекул (РАМР), и в частности единственный зарегистри-рованный в России в качестве лекарственного препарата синтетического МБАФ -глюкозами-нилмурамилдипептид (ГМДП) -иммуномоду- Поскольку активное действующее начало Ликопида -ГМДП, как высокоспецифический лиганд NOD2-рецептора врожденного имму-нитета, он способен вызывать активацию фак-тора транскрипции NF-kB и продукцию широ-кого спектра иммунорегуляторных цитокинов [17,19]. Поэтому представляют интерес работы по изучению влияния иммуномодулятора на па-тогенетический механизм аллергического IgE-опосредованного воспаления.…”