Synthesis, Formulation, and Adjuvanticity of Monodesmosidic Saponins with Olenanolic Acid, Hederagenin and Gypsogenin Aglycones, and some C-28 Ester Derivatives
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Synthesis, Formulation, and Adjuvanticity of Monodesmosidic Saponins with Olenanolic Acid, Hederagenin and Gypsogenin Aglycones, and some C-28 Ester Derivatives. / Greatrex, Ben W.; Daines, Alison M.; Hook, Sarah; Lenz, Dirk H.; McBurney, Warren; Rades, Thomas; Rendle, Phillip M.
In: ChemistryOpen, Vol. 4, No. 6, 12.2015, p. 740-755.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Synthesis, Formulation, and Adjuvanticity of Monodesmosidic Saponins with Olenanolic Acid, Hederagenin and Gypsogenin Aglycones, and some C-28 Ester Derivatives
AU - Greatrex, Ben W.
AU - Daines, Alison M.
AU - Hook, Sarah
AU - Lenz, Dirk H.
AU - McBurney, Warren
AU - Rades, Thomas
AU - Rendle, Phillip M.
PY - 2015/12
Y1 - 2015/12
N2 - 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(13)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(13)Glcp)hederagenin, was stimulatory at high concentrations in cell culture, but this did not translate to strong responses in vivo.
AB - 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(13)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(13)Glcp)hederagenin, was stimulatory at high concentrations in cell culture, but this did not translate to strong responses in vivo.
KW - carbohydrates
KW - glycosylation
KW - immunostimulatory effects
KW - saponins
KW - vaccine adjuvants
U2 - 10.1002/open.201500149
DO - 10.1002/open.201500149
M3 - Journal article
C2 - 27308200
VL - 4
SP - 740
EP - 755
JO - ChemistryOpen
JF - ChemistryOpen
SN - 2191-1363
IS - 6
ER -
ID: 162126542