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Synthesis and Immunological Evaluation of Mannosylated Desmuramyl Dipeptides Modified by Lipophilic Triazole Substituents

Muramyl dipeptide (N-acetylmuramyl-L-alanyl-D-isoglutamine, MDP) is the smallest peptidoglycan fragment able to trigger an immune response by activating the NOD2 receptor. Structural modification of MDP can lead to analogues with improved immunostimulating properties. The aim of this work was to pre...

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Autores principales: Petrović Peroković, Vesna, Car, Željka, Bušljeta, Mia, Mihelec, Danijela, Paurević, Marija, Ivanković, Siniša, Stojković, Ranko, Ribić, Rosana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368957/
https://www.ncbi.nlm.nih.gov/pubmed/35955759
http://dx.doi.org/10.3390/ijms23158628
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author Petrović Peroković, Vesna
Car, Željka
Bušljeta, Mia
Mihelec, Danijela
Paurević, Marija
Ivanković, Siniša
Stojković, Ranko
Ribić, Rosana
author_facet Petrović Peroković, Vesna
Car, Željka
Bušljeta, Mia
Mihelec, Danijela
Paurević, Marija
Ivanković, Siniša
Stojković, Ranko
Ribić, Rosana
author_sort Petrović Peroković, Vesna
collection PubMed
description Muramyl dipeptide (N-acetylmuramyl-L-alanyl-D-isoglutamine, MDP) is the smallest peptidoglycan fragment able to trigger an immune response by activating the NOD2 receptor. Structural modification of MDP can lead to analogues with improved immunostimulating properties. The aim of this work was to prepare mannosylated desmuramyl peptides (ManDMP) containing lipophilic triazole substituents to study their immunomodulating activities in vivo. The adjuvant activity of the prepared compounds was evaluated in the mouse model using ovalbumin as an antigen and compared to the MDP and referent adjuvant ManDMPTAd. The obtained results confirm that the α-position of D-isoGln is the best position for the attachment of lipophilic substituents, especially adamantylethyl triazole. Compound 6c exhibited the strongest adjuvant activity, comparable to the MDP and better than referent ManDMPTAd.
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spelling pubmed-93689572022-08-12 Synthesis and Immunological Evaluation of Mannosylated Desmuramyl Dipeptides Modified by Lipophilic Triazole Substituents Petrović Peroković, Vesna Car, Željka Bušljeta, Mia Mihelec, Danijela Paurević, Marija Ivanković, Siniša Stojković, Ranko Ribić, Rosana Int J Mol Sci Article Muramyl dipeptide (N-acetylmuramyl-L-alanyl-D-isoglutamine, MDP) is the smallest peptidoglycan fragment able to trigger an immune response by activating the NOD2 receptor. Structural modification of MDP can lead to analogues with improved immunostimulating properties. The aim of this work was to prepare mannosylated desmuramyl peptides (ManDMP) containing lipophilic triazole substituents to study their immunomodulating activities in vivo. The adjuvant activity of the prepared compounds was evaluated in the mouse model using ovalbumin as an antigen and compared to the MDP and referent adjuvant ManDMPTAd. The obtained results confirm that the α-position of D-isoGln is the best position for the attachment of lipophilic substituents, especially adamantylethyl triazole. Compound 6c exhibited the strongest adjuvant activity, comparable to the MDP and better than referent ManDMPTAd. MDPI 2022-08-03 /pmc/articles/PMC9368957/ /pubmed/35955759 http://dx.doi.org/10.3390/ijms23158628 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Petrović Peroković, Vesna
Car, Željka
Bušljeta, Mia
Mihelec, Danijela
Paurević, Marija
Ivanković, Siniša
Stojković, Ranko
Ribić, Rosana
Synthesis and Immunological Evaluation of Mannosylated Desmuramyl Dipeptides Modified by Lipophilic Triazole Substituents
title Synthesis and Immunological Evaluation of Mannosylated Desmuramyl Dipeptides Modified by Lipophilic Triazole Substituents
title_full Synthesis and Immunological Evaluation of Mannosylated Desmuramyl Dipeptides Modified by Lipophilic Triazole Substituents
title_fullStr Synthesis and Immunological Evaluation of Mannosylated Desmuramyl Dipeptides Modified by Lipophilic Triazole Substituents
title_full_unstemmed Synthesis and Immunological Evaluation of Mannosylated Desmuramyl Dipeptides Modified by Lipophilic Triazole Substituents
title_short Synthesis and Immunological Evaluation of Mannosylated Desmuramyl Dipeptides Modified by Lipophilic Triazole Substituents
title_sort synthesis and immunological evaluation of mannosylated desmuramyl dipeptides modified by lipophilic triazole substituents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368957/
https://www.ncbi.nlm.nih.gov/pubmed/35955759
http://dx.doi.org/10.3390/ijms23158628
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