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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Trained Immunity-Promoting Nanobiologic Therapy Suppresses Tumor Growth and Potentiates Checkpoint Inhibition.
Bram Priem,Mandy M. T. van Leent,Mandy M. T. van Leent,Abraham J. P. Teunissen,Alexandros Marios Sofias,Alexandros Marios Sofias,Vera P. Mourits,Lisa Willemsen,Emma D. Klein,Roderick S. Oosterwijk,Anu E. Meerwaldt,Anu E. Meerwaldt,Jazz Munitz,Geoffrey Prévot,Anna Vera D Verschuur,Sheqouia A. Nauta,Esther M. van Leeuwen,Elizabeth L. Fisher,Karen A.M. de Jong,Yiming Zhao,Yohana C. Toner,Georgios Soultanidis,Claudia Calcagno,Paul H. H. Bomans,Heiner Friedrich,Nico A. J. M. Sommerdijk,Thomas Reiner,Thomas Reiner,Raphaël Duivenvoorden,Raphaël Duivenvoorden,Eva Zupančič,Julie Di Martino,Ewelina Kluza,Mohammad Rashidian,Hidde L. Ploegh,Rick M. Dijkhuizen,Sjoerd Hak,Carlos Pérez-Medina,Carlos Pérez-Medina,Jose Javier Bravo-Cordero,Menno P.J. de Winther,Leo A. B. Joosten,Leo A. B. Joosten,Andrea van Elsas,Zahi A. Fayad,Alexander Rialdi,Denis Torre,Ernesto Guccione,Jordi Ochando,Jordi Ochando,Mihai G. Netea,Mihai G. Netea,Mihai G. Netea,Arjan W. Griffioen,Willem J. M. Mulder +54 more
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Journal ArticleDOI
Proteasomal degradation of Nod2 protein mediates tolerance to bacterial cell wall components.
TL;DR: It is shown that activation of Nod2 by its ligand, muramyl dipeptide in the bacterial cell wall, induces rapid degradation of NOD2, which confers MDP tolerance in vitro and in vivo, which indicates that TLRs and NLRs induce a tolerant state through distinct molecular mechanisms that protect the host from septic shock.
References
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Journal ArticleDOI
MDP‐induced interleukin‐1β processing requires Nod2 and CIAS1/NALP3
Qilin Pan,John C. Mathison,Colleen Fearns,Vladimir V. Kravchenko,Jean da Silva Correia,Hal M. Hoffman,Koichi Kobayashi,John Bertin,Ethan P. Grant,Anthony J. Coyle,Fayyaz S. Sutterwala,Yasunori Ogura,Richard A. Flavell,Richard J. Ulevitch +13 more
TL;DR: Using mice bearing selective gene deletions, in vitro and in vivo data are provided showing that MDP‐induced IL‐1β release requires Nod2 and CIAS1/NALP3 as well as receptor‐interacting protein‐2 (Rip2), apoptosis‐associated speck‐like protein containing a caspase activation and recruitment domain (ASC), and caspases‐1.
Journal ArticleDOI
Muramyl peptides. Chemical structure, biological activity and mechanism of action.
TL;DR: The conclusions of this review try to foresee the future applications of MDP and its derivatives, as components of vaccines, as anticancer and antiparasitic agents and ends with a word of caution concerning the possible side effects of the intensive use of immunomodulators in human beings.
Journal Article
Synergistic activation by recombinant mouse interferon-γ and muramyl dipeptide of tumoricidal properties in mouse macrophages
I Saiki,I J Fidler +1 more
TL;DR: The encapsulation of genetically engineered IFN-gamma and synthetically produced MDP within the same liposome is highly efficient in producing synergistic activation of tumoricidal properties in mouse macrophages.
Journal ArticleDOI
The NOD2-RICK Complex Signals from the Plasma Membrane
Patrick Lécine,Sophie Esmiol,Jean-Yves Metais,Cendrine Nicoletti,Claire Nourry,Christine McDonald,Gabriel Núñez,Jean-Pierre Hugot,Jean-Paul Borg,Vincent Ollendorff +9 more
TL;DR: It is demonstrated that membrane-bound versions of NOD2 and Crohn disease-associated mutants R702W and G908R are capable of responding to MDP and activating the NF-κB pathway from this location, and that endogenous RICK localizes at the plasma membrane in the THP1 cell line.
Journal Article
Immunoadjuvant activities of synthetic N-acetyl-muramyl-peptides or -amino acids.
TL;DR: The importance of the configuration of the glutamic acid residue or its amides, i.e. the presence of the D-isoglutamine residue in the N-acetylmuramyl-dipeptide, for manifestation of adjuvant activities in stimulation of both antibody-mediated and cell-mediated immune responses is indicated.