13343-62-9Relevant articles and documents
Regioselective Manipulation of GlcNAc Provides Allosamine, Lividosamine, and Related Compounds
Zhang, Ji,Eisink, Niek N.H.M.,Witte, Martin D.,Minnaard, Adriaan J.
, p. 516 - 525 (2019)
Palladium-catalyzed oxidation of isopropyl N-acetyl-α-d-glucosamine (GlcNAc) is used to prepare the rare sugars allosamine, lividosamine, and related compounds with unprecedented selectivity. The Passerini reaction applied on 3-keto-GlcNAc provides an ent
Membrane Association Dictates Ligand Specificity for the Innate Immune Receptor NOD2
Schaefer, Amy K.,Melnyk, James E.,Baksh, Michael M.,Lazor, Klare M.,Finn,Grimes, Catherine Leimkuhler
, p. 2216 - 2224 (2017)
The human gut must regulate its immune response to resident and pathogenic bacteria, numbering in the trillions. The peptidoglycan component of the bacterial cell wall is a dense and rigid structure that consists of polymeric carbohydrates and highly cross-linked peptides which offers protection from the host and surrounding environment. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), a human membrane-associated innate immune receptor found in the gut epithelium and mutated in an estimated 30% of Crohn's disease patients, binds to peptidoglycan fragments and initiates an immune response. Using a combination of chemical synthesis, advanced analytical assays, and protein biochemistry, we tested the binding of a variety of synthetic peptidoglycan fragments to wild-type (WT)-NOD2. Only when the protein was presented in the native membrane did binding measurements correlate with a NOD2-dependent nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) response, supporting the hypothesis that the native-membrane environment confers ligand specificity to the NOD2 receptor for NF-κB signaling. While N-acetyl-muramyl dipeptide (MDP) has been thought to be the minimal peptidoglycan fragment necessary to activate a NOD2-dependent immune response, we found that fragments with and without the dipeptide moiety are capable of binding and activating a NOD2-dependent NF-κB response, suggesting that the carbohydrate moiety of the peptidoglycan fragments is the minimal functional epitope. This work highlights the necessity of studying NOD2-ligand binding in systems that resemble the receptor's natural environment, as the cellular membrane and/or NOD2 interacting partners appear to play a crucial role in ligand binding and in triggering an innate immune response.
Synthesis of Bacterial-Derived Peptidoglycan Cross-Linked Fragments
Mashayekh, Siavash,Bersch, Klare L.,Ramsey, Jared,Harmon, Thomas,Prather, Benjamin,Genova, Lauren A.,Grimes, Catherine L.
supporting information, p. 16243 - 16253 (2020/11/13)
Peptidoglycan (PG) is the core structural motif of the bacterial cell wall. Fragments released from the PG serve as fundamental recognition elements for the immune system. The structure of the PG, however, encompasses a variety of chemical modifications among different bacterial species. Here, the applicability of organic synthetic methods to address this chemical diversity is explored, and the synthesis of cross-linked PG fragments, carrying biologically relevant amino acid modifications and peptide cross-linkages, is presented using solution and solid phase approaches.
NOVEL MURAMYL PEPTIDE DERIVATIVE COMPOUND, SYNTHESIS AND USES THEREOF
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Paragraph 0173, (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.
