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

Title
Synthesis, Formulation, and Adjuvanticity of Monodesmosidic Saponins with Olenanolic Acid, Hederagenin and Gypsogenin Aglycones, and some C-28 Ester Derivatives
Publication Date
2015
Author(s)
Greatrex, Ben
( author )
OrcID: https://orcid.org/0000-0002-0356-4966
Email: bgreatre@une.edu.au
UNE Id une-id:bgreatre
Daines, Alison M
Hook, Sarah
Lenz, Dirk H
McBurney, Warren
Rades, Thomas
Rendle, Phillip M
Type of document
Journal Article
Language
en
Entity Type
Publication
Publisher
Wiley-VCH Verlag GmbH & Co KGaA
Place of publication
Germany
DOI
10.1002/open.201500149
UNE publication id
une:18797
Abstract
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-(Man'p'(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-(Man'p'(1→3)Glcp)hederagenin, was stimulatory at high concentrations in cell culture, but this did not translate to strong responses in vivo.
Link
Citation
ChemistryOpen, 4(6), p. 740-755
ISSN
2191-1363
Start page
740
End page
755

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