Structure of the saponin adjuvant QS-21 and its base-catalyzed isomerization product by 1H and natural abundance 13C NMR spectroscopy.
The saponin QS-21, derived from the bark of the Quillaja saponaria Molina tree, has shown great potential as an adjuvant with a number of vaccines. Kinetic studies carried out to establish the stability of vaccine formulations show that commercially supplied QS-21 (primarily QS-21A) is converted slowly at pH 5.5, and rapidly at higher pH, to an equilibrium mixture of two regioisomers, QS-21A and QS-21B, in a ratio of 20:1. NMR studies show that QS-21A and QS-21B differ only in the point of attachment of the fatty acyl moiety to the fucose sugar ring. The major isomer, QS-21A, has the fatty acyl portion attached at the 4-hydroxyl group whereas the minor isomer, QS-21B, has the fatty acyl portion attached at the 3-hydroxyl group. The isomerization most likely involves ionization of the 3-hydroxy group and intramolecular acyl transfer from the 4-hydroxy group. The relative stereochemistry of the triterpene and the sugar anomeric centers is also established by NMR methods.
Jacobsen
N E
NE
Genentech, Inc., South San Francisco, CA 94080, USA.
Fairbrother
W J
WJ
Kensil
C R
CR
Lim
A
A
Wheeler
D A
DA
Powell
M F
MF
D000276:Adjuvants, Immunologic / Q000737:chemistry*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002851:Chromatography, High Pressure Liquid; D005227:Fatty Acids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry; D012503:Saponins / Q000737:chemistry*; D013237:Stereoisomerism; D013729:Terpenes / Q000737:chemistry
D000276:Adjuvants, Immunologic; D005227:Fatty Acids; D009844:Oligosaccharides; D012503:Saponins; D013729:Terpenes; C078785:saponin QA-21V1