Synthesis, Formulation, and Adjuvanticity of Monodesmosidic Saponins with Olenanolic Acid, Hederagenin and Gypsogenin Aglycones, and some C-28 Ester Derivatives.
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.
Ferrier Research Institute Victoria University of Wellington Gracefield Rd Lower Hutt 5010 New Zealand; School of Science & Technology University of New England Armidale NSW 2351 Australia.
Ben W
0000-0002-0356-4966
BW
Greatrex
Ferrier Research Institute Victoria University of Wellington Gracefield Rd Lower Hutt 5010 New Zealand.
Alison M
AM
Daines
School of Pharmacy University of Otago Dunedin 9016 New Zealand.
Sarah
S
Hook
Ferrier Research Institute Victoria University of Wellington Gracefield Rd Lower Hutt 5010 New Zealand.
Dirk H
DH
Lenz
School of Pharmacy University of Otago Dunedin 9016 New Zealand.
Warren
W
McBurney
School of Pharmacy University of Otago Dunedin 9016 New Zealand.
Thomas
0000-0002-7521-6020
T
Rades
Ferrier Research Institute Victoria University of Wellington Gracefield Rd Lower Hutt 5010 New Zealand.
Phillip M
0000-0002-2825-8746
PM
Rendle
carbohydrates; glycosylation; immunostimulatory effects; saponins; vaccine adjuvants