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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Liposomes as vaccine delivery systems: a review of the recent advances
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Peptide-based cancer therapy: Opportunity and challenge
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Therapeutic targeting of trained immunity
Willem J. M. Mulder,Jordi Ochando,Jordi Ochando,Leo A. B. Joosten,Leo A. B. Joosten,Zahi A. Fayad,Mihai G. Netea,Mihai G. Netea +7 more
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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Journal ArticleDOI
Synthesis and biological activity of aryl S -β-glycosides of 1-thio- N -acetylmuramyl- L -alanyl- D -isoglutamine
A. E. Zemlyakov,V. N. Tsikalova,Liana R. Azizova,V. Ya. Chirva,E. L. Mulik,M. V. Shkalev,O. V. Kalyuzhin,M. V. Kiselevsky +7 more
TL;DR: The reliable induction of the spontaneous activity of natural killers in the population of blood mononuclear cells was observed only for phenyl β-thio-MDP at a dose of 200 µg/ml.
Journal ArticleDOI
[Synthesis and protective anti-infective action of anomeric lipophilic glycosides of N-acetylmuramyl-L-alanyl-D-isoglutamine].
TL;DR: No reliable differences between the stimulation of mouse resistance to the infection with Staphylococcus aureus and Escherichia coli with the MDP α-and β-glycosides were found.