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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Therapeutic targeting of trained immunity
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TL;DR: The mechanisms responsible for the induction of trained immunity are described and strategies to regulate it are proposed as a potential treatment of immune-related diseases.
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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
TL;DR: It is shown that rationally designed nanobiologics can promote trained immunity and elicit a durable anti-tumor response either as a monotherapy or in combination with checkpoint inhibitor drugs.
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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Chemical conjugation of muramyl dipeptide and paclitaxel to explore the combination of immunotherapy and chemotherapy for cancer
TL;DR: Conjugate at 2'-O position demonstrates both antitumor activity and synergism bewteen the effects of muramyl dipeptide and paclitaxel for activating mouse peritoneal macrophages.
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Muramyl dipeptide (MDP) synergizes with interleukin 2 and interleukin 4 to stimulate, respectively, the differentiation and proliferation of B cells.
TL;DR: MDP appears to amplify cytokine effects in B cell activation, by a mechanism which does not appear to involve free calcium mobilization, in contrast to previous work on single interleukins.
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N-(trans-2-[[2'-(acetylamino)cyclohexyl]oxy]acetyl}-L-alanyl-D-glutamic acid : A novel immunologically active carbocyclic muramyl dipeptide analogue
Danijel Kikelj,Slavko Pečar,Vladimir Kotnik,Anton Stalc,Branka Wraber-Herzog,Saša Simčič,Alojz Ihan,Lidija Mag. Klamfer,Lucka Povsic,Rok Grahek,Elizabeta Suhadolc,Mirjam Hočevar,Helmut Hönig,Renate Rogi-Kohlenprath +13 more
TL;DR: This novel nor-MDP analogue protects mice against the immunosuppressive effect of cyclophosphamide and increases the nonspecific resistance of mice against fungal infection.
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Enhancement by muramyl peptides of the protective response of interferon-α/β against encephalomyocarditis virus infection
TL;DR: It is suggested that combination therapy with safe muramyl peptides and IFN-α/β could constitute a highly effective and new regimen for the treatment of viral infections in humans.
Journal ArticleDOI
Structural characteristics of peptidoglycan fragments required to prime mice for induction of anaphylactoid reactions by lipopolysaccharides.
TL;DR: Structural characteristics of peptidoglycan fragments required to prime mice for the induction of anaphylactoid reactions by Salmonella abortusequi lipopolysaccharide were examined in endotoxin-resistant C3H/HeJ mice with special focus on the disaccharide-pentapeptide.