18800-73-2Relevant articles and documents
Synthesis of Carbapenems Containing Peptidoglycan Mimetics and Inhibition of the Cross-Linking Activity of a Transpeptidase of l,d Specificity
Saidjalolov, Saidbakhrom,Edoo, Zainab,Fonvielle, Matthieu,Mayer, Louis,Iannazzo, Laura,Arthur, Michel,Etheve-Quelquejeu, Mélanie,Braud, Emmanuelle
supporting information, p. 3542 - 3551 (2021/02/05)
The carbapenem class of β-lactams has been optimized against Gram-negative bacteria producing extended-spectrum β-lactamases by introducing substituents at position C2. Carbapenems are currently investigated for the treatment of tuberculosis as these drugs are potent covalent inhibitors of l,d-transpeptidases involved in mycobacterial cell wall assembly. The optimization of carbapenems for inactivation of these unusual targets is sought herein by exploiting the nucleophilicity of the C8 hydroxyl group to introduce chemical diversity. As β-lactams are structure analogs of peptidoglycan precursors, the substituents were chosen to increase similarity between the drug and the substrate. Fourteen peptido-carbapenems were efficiently synthesized. They were more effective than the reference drug, meropenem, owing to the positive impact of a phenethylthio substituent introduced at position C2 but the peptidomimetics added at position C8 did not further improve the activity. Thus, position C8 can be modified to modulate the pharmacokinetic properties of highly efficient carbapenems.
Further Insights on Structural Modifications of Muramyl Dipeptides to Study the Human NOD2 Stimulating Activity
Cheng, Wei-Chieh,You, Ting-Yun,Teo, Zhen-Zhuo,Sayyad, Ashik A.,Maharana, Jitendra,Guo, Chih-Wei,Liang, Pi-Hui,Lin, Chung-Shun,Meng, Fan-Chun
supporting information, p. 3836 - 3844 (2020/10/21)
A series of muramyl dipeptide (MDP) analogues with structural modifications at the C4 position of MurNAc and on the d-iso-glutamine (isoGln) residue of the peptide part were synthesized. The C4-diversification of MurNAc was conveniently achieved by using CuAAC click strategy to conjugate an azido muramyl dipeptide precursor with structurally diverse alkynes. d-Glutamic acid (Glu), replaced with isoGln, was applied for the structural diversity through esterification or amidation of the carboxylic acid. In total, 26 MDP analogues were synthesized and bio-evaluated for the study of human NOD2 stimulation activity in the innate immune response. Interestingly, MDP derivatives with an ester moiety are found to be more potent than reference compound MDP itself or MDP analogues containing an amide moiety. Among the varied lengths of the alkyl chain in ester derivatives, the MDP analogue bearing the d-glutamate dodecyl (C12) ester moiety showed the best NOD2 stimulation potency.
NOVEL MURAMYL PEPTIDE DERIVATIVE COMPOUND, SYNTHESIS AND USES THEREOF
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Paragraph 0163; 0169, (2019/01/04)
The invention relates to novel Muramyl Dipeptide (MDP) derivative compound of structural Formula-VIII, a process for synthesis, intermediates used in the synthesis and use thereof; wherein R1 and R2 both are hydrogen; or R1 is hydrogen and R2 is alkyl or aryl; or R1 is alkyl or aryl and R2 is hydrogen; or R1 and R2 both are alkyl or aryl (same or different groups); wherein alkyl group constitute C1-C6 alkyl or higher (both linear and branched) with or without heteroatoms; and aryl group constitute phenyl, substituted phenyl, heteraryl, arylalkyl and polynuclear aromatics. These compounds possess excellent pharmacological properties, in particular immunomodulating properties for use as adjuvant in vaccine formulations. These compounds are, particularly useful as adjuvants in vaccines.
Critical Impact of Peptidoglycan Precursor Amidation on the Activity of l,d-Transpeptidases from Enterococcus faecium and Mycobacterium tuberculosis
Ngadjeua, Flora,Braud, Emmanuelle,Saidjalolov, Saidbakhrom,Iannazzo, Laura,Schnappinger, Dirk,Ehrt, Sabine,Hugonnet, Jean-Emmanuel,Mengin-Lecreulx, Dominique,Patin, Delphine,Ethève-Quelquejeu, Mélanie,Fonvielle, Matthieu,Arthur, Michel
supporting information, p. 5743 - 5747 (2018/02/26)
The bacterial cell wall peptidoglycan contains unusual l- and d-amino acids assembled as branched peptides. Insight into the biosynthesis of the polymer has been hampered by limited access to substrates and to suitable polymerization assays. Here we report the full synthesis of the peptide stem of peptidoglycan precursors from two pathogenic bacteria, Enterococcus faecium and Mycobacterium tuberculosis, and the development of a sensitive post-derivatization assay for their cross-linking by l,d-transpeptidases. Access to series of stem peptides showed that amidation of free carboxyl groups is essential for optimal enzyme activity, in particular the amidation of diaminopimelate (DAP) residues for the cross-linking activity of the l,d-transpeptidase LdtMt2 from M. tuberculosis. Accordingly, construction of a conditional mutant established the essential role of AsnB indicating that this DAP amidotransferase is an attractive target for the development of anti-mycobacterial drugs.
NOVEL MURAMYL PEPTIDE DERIVATIVE COMPOUND, SYNTHESIS AND USES THEREOF
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Page/Page column 18; 33, (2017/06/30)
The invention relates to novel Muramyl Dipeptide (MDP) derivative compound of structural Formula-VIII, a process for synthesis, intermediates used in the synthesis and use thereof. R = alkyl (both linear and branched), aryl, substituted aryl, alkoxy alkyl Wherein, R can be both linear and branched alkyl, aryl, substituted aryl and alkoxy alkyl. These compounds possess excellent pharmacological properties, in particular immunomodulating properties for use as adjuvant in vaccine formulations. These compounds are, particularly useful as adjuvants in vaccines.
CHEMICAL SYNTHESIS AND ANTI-TUMOR AND ANTI-METASTATIC EFFECTS OF DUAL FUNCTIONAL CONJUGATE
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Paragraph 0125-0130, (2017/10/24)
The present invention discloses chemical synthesis, anti-tumor and anti-metastatic effects of a dual functional conjugate as showed by formula I. In detail, paclitaxel or docetaxol is linked with muramyl dipeptide derivative to form a conjugate, thus dual anti-tumor and anti-metastatic effects are achieved by combination of chemotherapy and immunotherapy. The present invention also discloses that paclitaxel or docetaxol and muramyl dipeptide derivative conjugate is synthesized by combination of solid-phase and solution-phase synthesis, and said conjugate can be used in manufacture of anti-tumor medicaments as proved by reliable bioassays.
Convergent synthesis of novel muramyl dipeptide analogues: Inhibition of porphyromonas gingivalis-induced pro-inflammatory effects by high doses of muramyl dipeptide
Cai, Bin,Panek, James S.,Amar, Salomon
, p. 6878 - 6890 (2016/08/05)
Porphyromonas gingivalis (P.g.)-induced TNF-α can be affected by muramyl dipeptide (MDP) in a biphasic concentration-dependent manner. We found that in P.g.-exposed macrophages, treatment with 10 μg/mL of MDP (MDP-low) up-regulated TNF-α by 29%, while 100
Solution-phase synthesis of a muramyl dipeptide analogue MDA
Zhao, Nan,Ma, Yao,Liu, Gang
, p. 1443 - 1446 (2012/06/04)
The solution-phase synthesis of a muramyl dipeptide (MDP) analogue of Nα-[4-chlorocinnamoyl-l-alanyl-d-isoglutaminyl]-l-lysine (MDA, 2) is reported that possesses the features of easy feasibility, safety and low cost in large scale of synthesis.
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 and neuroprotective activity of analogues of glycyl-L-prolyl-L- glutamic acid (GPE) modified at the α-carboxylic acid
Trotter, Nicholas S.,Brimble, Margaret A.,Harris, Paul W.R.,Callis, David J.,Sieg, Frank
, p. 501 - 517 (2007/10/03)
The synthesis of nine GPE* analogues, wherein the α-carboxylic acid group of glutamic acid has been modified, is described by coupling readily accessible N-benzyloxycarbonyl-glycyl-l-proline 2 with various analogues of glutamic acid. Pharmacological evaluation of the novel compounds was undertaken to further understand the role of the glutamate residue on the observed neuroprotective properties of the endogenous tripeptide GPE.
