Multivalent, Stabilized Mannose-6-Phosphates for the Targeted Delivery of Toll-Like Receptor Ligands and Peptide Antigens
© 2020 The Authors. Published by Wiley-VCH GmbH..
Mannose-6-phosphate (M6P) is recognized by the mannose-6-phosphate receptor and plays an important role in the transport of cargo to the endosomes, making it an attractive tool to improve endosomal trafficking of vaccines. We describe herein the assembly of peptide antigen conjugates carrying clusters of mannose-6-C-phosphonates (M6Po). The M6Po's are stable M6P mimics that are resistant to cleavage of the phosphate group by endogenous phosphatases. Two different strategies for the incorporation of the M6Po clusters in the conjugate have been developed: the first relies on a "post-assembly" click approach employing an M6Po bearing an alkyne functionality; the second hinges on an M6Po C-glycoside amino acid building block that can be used in solid-phase peptide synthesis. The generated conjugates were further equipped with a TLR7 ligand to stimulate dendritic cell (DC) maturation. While antigen presentation is hindered by the presence of the M6Po clusters, the incorporation of the M6Po clusters leads to increased activation of DCs, thus demonstrating their potential in improving vaccine adjuvanticity by intraendosomally active TLR ligands.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
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| Enthalten in: |
Chembiochem : a European journal of chemical biology - 22(2021), 2 vom: 15. Jan., Seite 434-440 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Reintjens, Niels R M [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.09.2021 Date Revised 10.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/cbic.202000538 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM314379568 |
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| 100 | 1 | |a Reintjens, Niels R M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Multivalent, Stabilized Mannose-6-Phosphates for the Targeted Delivery of Toll-Like Receptor Ligands and Peptide Antigens |
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| 500 | |a Date Revised 10.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020 The Authors. Published by Wiley-VCH GmbH. | ||
| 520 | |a Mannose-6-phosphate (M6P) is recognized by the mannose-6-phosphate receptor and plays an important role in the transport of cargo to the endosomes, making it an attractive tool to improve endosomal trafficking of vaccines. We describe herein the assembly of peptide antigen conjugates carrying clusters of mannose-6-C-phosphonates (M6Po). The M6Po's are stable M6P mimics that are resistant to cleavage of the phosphate group by endogenous phosphatases. Two different strategies for the incorporation of the M6Po clusters in the conjugate have been developed: the first relies on a "post-assembly" click approach employing an M6Po bearing an alkyne functionality; the second hinges on an M6Po C-glycoside amino acid building block that can be used in solid-phase peptide synthesis. The generated conjugates were further equipped with a TLR7 ligand to stimulate dendritic cell (DC) maturation. While antigen presentation is hindered by the presence of the M6Po clusters, the incorporation of the M6Po clusters leads to increased activation of DCs, thus demonstrating their potential in improving vaccine adjuvanticity by intraendosomally active TLR ligands | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a mannose-6-phosphate receptor | |
| 650 | 4 | |a peptide conjugates | |
| 650 | 4 | |a solid-phase peptide synthesis | |
| 650 | 7 | |a Antigens |2 NLM | |
| 650 | 7 | |a Ligands |2 NLM | |
| 650 | 7 | |a Mannosephosphates |2 NLM | |
| 650 | 7 | |a Peptides |2 NLM | |
| 650 | 7 | |a Toll-Like Receptors |2 NLM | |
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| 700 | 1 | |a Tondini, Elena |e verfasserin |4 aut | |
| 700 | 1 | |a Vis, Christopher |e verfasserin |4 aut | |
| 700 | 1 | |a McGlinn, Toroa |e verfasserin |4 aut | |
| 700 | 1 | |a Meeuwenoord, Nico J |e verfasserin |4 aut | |
| 700 | 1 | |a Hogervorst, Tim P |e verfasserin |4 aut | |
| 700 | 1 | |a Overkleeft, Herman S |e verfasserin |4 aut | |
| 700 | 1 | |a Filippov, Dmitri V |e verfasserin |4 aut | |
| 700 | 1 | |a van der Marel, Gijsbert A |e verfasserin |4 aut | |
| 700 | 1 | |a Ossendorp, Ferry |e verfasserin |4 aut | |
| 700 | 1 | |a Codée, Jeroen D C |e verfasserin |4 aut | |
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