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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9368957 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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