Muramyl dipeptide and its derivatives: peptide adjuvant in immunological disorders and cancer therapy.
TLDR
The structural modifications of MDP and its derivatives have been extensively studied in an attempt to increase adjuvant activity and boost the immune response effectively for clinical use in the treatment of cancer and other diseases.Abstract:
Muramyl dipeptide (MDP) is a synthetic immunoreactive peptide consisting of N-acetyl muramic acid attached to a short amino acid chain of L-Ala-D-isoGln. It was first identified in bacterial cell wall peptidoglycan as an active component in Freund's complete adjuvant. In the cell, MDP is detected by NOD2, a cytoplasmic receptor belonging to the human innate immune system. NOD2 mutations are frequently observed in patients with Crohn's disease, an autoimmune disorder, suggesting the significance of the MDP-NOD2 pathway in activating immunity. For this reason, structural modifications of MDP and its derivatives have been extensively studied in an attempt to increase adjuvant activity and boost the immune response effectively for clinical use in the treatment of cancer and other diseases. This review summarizes the synthetic chemistry of MDP and its derivatives and discusses their pharmacological action and stereoselective synthesis.read more
Citations
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Synthesis and Application of Methyl N,O-Hydroxylamine Muramyl Peptides
TL;DR: Methyl N,O‐hydroxylamine linkers are incorporated onto a synthetic PG derivative, muramyl dipeptide (MDP), and this methodology provides rapid access to PG probes in one step and allows for the installation of a variety of chemical handles to advance the molecular understanding of PG and the innate immune system.
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Modulation of the NOD-like receptors NOD1 and NOD2: A chemist's perspective
Elizabeth A. D'Ambrosio,Walter R. Drake,Siavash Mashayekh,Ophelia I. Ukaegbu,Ashley R Brown,Catherine L. Grimes +5 more
TL;DR: A chemist's perspective on some of the most crucial and complex components of two receptors (NOD1 and NOD2): starting from the structural and chemical characteristics of bacterial-derived small molecules, to the specific proposed models of molecular recognition of these molecules by immune receptors, and the subsequent post-translational modifications that ultimately dictate downstream immune signaling.
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Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides
Rosana Ribić,Ranko Stojković,Lidija Milković,Mariastefania Antica,Marko Cigler,Srđanka Tomić +5 more
TL;DR: The design, synthesis and biological evaluation of novel mannosylated desmuramyl peptide derivatives are presented and the strongest enhancement of IgG production was stimulated by compound 21 (Man-OCH2-ᴅ-(1-Ad)Gly-ʟ-Ala- ᴅ-isoGln).
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Exploring the chemical space of peptides for drug discovery: a focus on linear and cyclic penta-peptides
TL;DR: The physicochemical property profile and chemical space of four synthetic linear and cyclic combinatorial peptide libraries are reported to support that synthetic penta-peptides are suitable compounds to be used in drug discovery projects.
References
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Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease
Jean-Pierre Hugot,Mathias Chamaillard,Mathias Chamaillard,Habib Zouali,Suzanne Lesage,Jean-Pierre Cézard,Jacques Belaiche,Sven Almer,Curt Tysk,Colm O'Morain,Miquel A. Gassull,Vibeke Binder,Yigael Finkel,Antoine Cortot,Robert Modigliani,Pierre Laurent-Puig,C. Gower-Rousseau,J. Macry,Jean-Frederic Colombel,Mourad Sahbatou,Gilles Thomas,Gilles Thomas +21 more
TL;DR: It is suggested that the NOD2 gene product confers susceptibility to Crohn's disease by altering the recognition of these components and/or by over-activating NF-kB in monocytes, thus documenting a molecular model for the pathogenic mechanism of Crohn’s disease that can now be further investigated.
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Inflammatory bowel disease: Etiology and pathogenesis
TL;DR: No single agent or distinct mechanism is the sine qua non motive that explains all aspects of IBD, and several distinguishing factors are likely necessary to result in either CD or UC; this review will attempt to discuss those that currently appear important.
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Peptidoglycan structure and architecture
TL;DR: In several species examined, the fine structure of the peptidoglycan significantly varies with the growth conditions, and the different models for the architecture are discussed with respect to structural and physical parameters.
Journal ArticleDOI
The immunological and genetic basis of inflammatory bowel disease.
G. Bouma,G. Bouma,Warren Strober +2 more
TL;DR: The most important finding is the identification of mutations in the gene that encodes NOD2 (nucleotide-binding oligomerization domain 2) protein in a subgroup of patients with Crohn's disease.
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Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract.
Koichi Kobayashi,Mathias Chamaillard,Yasunori Ogura,Octavian Henegariu,Naohiro Inohara,Gabriel Núñez,Richard A. Flavell +6 more
TL;DR: It is shown that protective immunity mediated by Nod2 recognition of bacterial muramyl dipeptide is abolished in Nod1-deficient mice, providing a possible mechanism for Nod 2 mutations in CD.