期刊
GLYCOBIOLOGY
卷 23, 期 10, 页码 1164-1174出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/glycob/cwt053
关键词
adjuvant; carbohydrate; inulin; isoform; vaccine
资金
- US Department of Health and Human Services [HHSN2722 00800039C]
- National Institutes of Health (NIH) [U01AI061142]
- Australian Research Council through a Linkage grant [LP0882596]
- Australian Research Council through a LIEF grant [LE0668489]
- Australian Research Council [LE0668489, LP0882596] Funding Source: Australian Research Council
In studying the molecular basis for the potent immune activity of previously described gamma and delta inulin particles and to assist in production of inulin adjuvants under Good Manufacturing Practice, we identified five new inulin isoforms, bringing the total to seven plus the amorphous form. These isoforms comprise the step-wise inulin developmental series amorphous -> alpha-1 (AI-1) -> alpha-2 (AI-2) -> gamma (GI) -> delta (DI) -> zeta (ZI) -> epsilon (EI) -> omega (OI) in which each higher isoform can be made either by precipitating dissolved inulin or by direct conversion from its precursor, both cases using regularly increasing temperatures. At higher temperatures, the shorter inulin polymer chains are released from the particle and so the key difference between isoforms is that each higher isoform comprises longer polymer chains than its precursor. An increasing trend of degree of polymerization is confirmed by end-group analysis using H-1 nuclear magnetic resonance spectroscopy. Inulin isoforms were characterized by the critical temperatures of abrupt phase-shifts (solubilizations or precipitations) in water suspensions. Such (aqueous) melting or freezing points are diagnostic and occur in strikingly periodic steps reflecting quantal increases in noncovalent bonding strength and increments in average polymer lengths. The (dry) melting points as measured by modulated differential scanning calorimetry similarly increase in regular steps. We conclude that the isoforms differ in repeated increments of a precisely repeating structural element. Each isoform has a different spectrum of biological activities and we show the higher inulin isoforms to be more potent alternative complement pathway activators.
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