Regiospecific glycosylation of immune potentiators: a novel platform for modifying adjuvant activity. (360G-Wellcome-085655_Z_08_Z)

£219,242

Adjuvants represent blunt tools to manipulate immunogenicity, with few molecular approaches available to selectively tune activity profiles. We have developed a unique biocatalysis system, based on glycosyltransferases from arabidopsis, that can regioselectively glycosylate small molecule immune potentiators. We have shown that for two polyphenols, regiospecific glucosylation alters bioactivity on dendritic cells (measured by differential regulation of CD40, CD80 and IL-6). We propose to exte nd these observations, using scalable in vitro assays to measure additional parameters of dendritic cell activation (including high content screening of cytoskeletal morphology), and adoptive transfer and immunization experiments. These studies will provide data to validate the concept that regiospecific glycosylation can optimize the functionality of small molecule immune potentiators. Over two-years, we will synthesize 20 regioselective mono- and di-glycosides based on 4 scaffolds. For each new glycoside, we will be able to interrogate an expanding database and determine whether our assays, alone or in combination, constitute a predictive algorithm for in vivo activity and the effects of glycosylation. This Project will provide the foundation for evaluating a broader range of scaffolds and an extended platform of GTs, as well as a basis for future studies on the mechanism(s) underlying these regioselective effects on scaffold activity.

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Grant Details

Amount Awarded 219242
Applicant Surname Kaye
Approval Committee Immunology and Infectious Disease Funding Committee
Award Date 2008-07-01T00:00:00+00:00
Financial Year 2007/08
Grant Programme: Title Project Grant
Internal ID 085655/Z/08/Z
Lead Applicant Prof Paul Kaye
Other Applicant(s) Dr Eng-Kiat Lim, Prof Dianna Bowles
Partnership Value 219242
Planned Dates: End Date 2011-03-31T00:00:00+00:00
Planned Dates: Start Date 2008-09-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Yorkshire and the Humber