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Synthesis, Formulation, and Adjuvanticity of Monodesmosidic Saponins with Olenanolic Acid, Hederagenin and Gypsogenin Aglycones, and some C-28 Ester Derivatives

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posted on 20.10.2020, 02:50 by BW Greatrex, Alison Daines, S Hook, DH Lenz, W McBurney, T Rades, Phillip Rendle
© 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. In an attempt to discover a new synthetic vaccine adjuvant, the glycosylation of hederagenin, gypsogenin, and oleanolic acid acceptors with di- and trisaccharide donors to generate a range of mimics of natural product QS-21 was carried out. The saponins were formulated with phosphatidylcholine and cholesterol, and the structures analyzed by transmission electron microscopy. 3-O-(Manp(1→3)Glcp)hederagenin was found to produce numerous ring-like micelles when formulated, while C-28 choline ester derivatives preferred self-assembly and did not interact with the liposomes. When alone and in the presence of cholesterol and phospholipid, the choline ester derivatives produced nanocrystalline rods or helical micelles. The effects of modifying sugar stereochemistry and the aglycone on the immunostimulatory effects of the saponins was then evaluated using the activation markers MHC class II and CD86 in murine bone marrow dendritic cells. The most active saponin, 3-O-(Manp(1→3)Glcp)hederagenin, was stimulatory at high concentrations in cell culture, but this did not translate to strong responses in vivo.

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Preferred citation

Greatrex, B. W., Daines, A. M., Hook, S., Lenz, D. H., McBurney, W., Rades, T. & Rendle, P. M. (2015). Synthesis, Formulation, and Adjuvanticity of Monodesmosidic Saponins with Olenanolic Acid, Hederagenin and Gypsogenin Aglycones, and some C-28 Ester Derivatives. ChemistryOpen, 4(6), 740-755. https://doi.org/10.1002/open.201500149

Journal title

ChemistryOpen

Volume

4

Issue

6

Publication date

01/12/2015

Pagination

740-755

Publisher

Wiley

Publication status

Published

Contribution type

Article

Online publication date

30/09/2015

ISSN

2191-1363

eISSN

2191-1363

Language

en

Exports