18814-50-1Relevant articles and documents
Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides
Ribi?, Rosana,Stojkovi?, Ranko,Milkovi?, Lidija,Antica, Mariastefania,Cigler, Marko,Tomi?, Sr?anka
, p. 1805 - 1814 (2019)
Muramyl dipeptide is the minimal structure of peptidoglycan with adjuvant properties. Replacement of the N-acetylmuramyl moiety and increase of lipophilicity are important approaches in the preparation of muramyl dipeptide analogues with improved pharmacological properties. Mannose receptors present on immunocompetent cells are pattern-recognition receptors and by mannose ligands binding they affect the immune system. Here we present the design, synthesis and biological evaluation of novel mannosylated desmuramyl peptide derivatives. Mannose was coupled to dipeptides containing a lipophilic adamantane on N- or C-terminus through a glycolyl or hydroxyisobutyryl linker. Adjuvant activities of synthesized compounds were investigated in the mouse model using ovalbumin as an antigen. Their activities were compared to the previously described mannosylated adamantane-containing desmuramyl peptide and peptidoglycan monomer. Tested compounds exhibited adjuvant activity and the strongest enhancement of IgG production was stimulated by compound 21 (Man-OCH2-(1-Ad)Gly-Ala-isoGln).
Activation for catalysis of penicillin-binding protein 2a from methicillin-resistant Staphylococcus aureus by bacterial cell wall
Fuda, Cosimo,Hesek, Dusan,Lee, Mijoon,Morio, Ken-Ichiro,Nowak, Thomas,Mobashery, Shahriar
, p. 2056 - 2057 (2007/10/03)
Methicillin-resistant Staphylococcus aureus (MRSA) has acquired a unique penicillin-binding protein (PBP), PBP 2a, which has rendered the organism resistant to the action of all available β-lactam antibiotics. The X-ray structure of PBP 2a shows the active site in a closed conformation, consistent with resistance to inhibition by β-lactam antibiotics. However, it is known that PBP 2a avidly cross-links the S. aureus cell wall, which is its physiological function. It is shown herein that synthetic fragments of the bacterial cell wall bind in a saturable manner to PBP 2a and cause a conformational change in the protein that makes the active site more accessible to binding to a β-lactam antibiotic. These observations and measurements point to a novel strategy by nature to keep the active site of PBP 2a sheltered from the inhibitory activity of the antibiotics, yet it becomes available to the polymeric cell wall by a requisite conformational change for the critical cell wall cross-linking reaction. Copyright
SYNTHESIS OF PEPTIDES, GLYCO DERIVATIVES AND GLYCOPEPTIDES FROM BACTERIAL CELL WALLS
Zaoral, Milan,Jezek, Jan,Krchnak, Viktor,Straka, Radovan
, p. 1424 - 1446 (2007/10/02)
Synthesis in solution and in solid phase was used to prepare alanyl-D-isoglutamine (VI), alanyl-D-isoglutaminyl-Nε-p-toluenesulfonyl-lysyl-D-alanine methyl ester (XIII), alanyl-D-isoglutaminyl-Nε-acetyl-lysyl-D-alanine methyl ester (XIV), alanyl-D-isoglutaminyl-Nε-acetyl-lysyl-D-alanyl-pentaglycine methyl ester and amide (XXXI, XXXII), methyl ester (XXXV), methyl ester (XXXVII), N-acetylmuramyl-alanyl-D-isoglutaminyl-Nε-acetyl-lysyl-D-alanyl-pentaglycine amide (XXXIX), methyl ester (XLI), and methyl ester (XLIII).Thetetrapeptides, nonapeptides, and tridecapeptides show a pronounced pyrogenic effect.Imunoadjuvant activity was observed not only with the glycopeptides but also with nonapeptide XXXI.
