Synthesis of archaeal glycolipid adjuvants-what is the optimum number of sugars?: Carbohydr.Res.

  1. Get@NRC: Synthesis of archaeal glycolipid adjuvants-what is the optimum number of sugars?: Carbohydr.Res. (Opens in a new window)
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Journal titleCarbohydr.Res.
Pages23492360; # of pages: 12
SubjectAdjuvants,Immunologic; Animals; binding; Canada; Carbohydrate Sequence; CD8-Positive T-Lymphocytes; cell; CELLS; chemical synthesis; chemistry; donor; Female; Form; glycolipid; Glycolipids; Halobacterium salinarum; Hydrolysis; immunology; lectin; lipid; Lipids; Liposomes; Mannose; Mice; Mice,Inbred C57BL; Molar; Molecular Sequence Data; Multiple; Ovalbumin; receptor; SERIES; sugar; SUGARS; Synthesis; UNIT; yield
AbstractAs part of a programme to optimize the use of archaeal-lipid liposomes (archaeosomes) as vaccine adjuvants, we present the synthesis and immunological testing of an oligomeric series of mannose glycolipids (Manp(1-5)). To generate the parent archaeol alcohol precursor, the polar lipids extracted from the archaeon Halobacterium salinarum were hydrolyzed to remove polar head groups, and the archaeol so generated partitioned into diethyl ether. This alcohol was then iteratively glycosylated with the donor 2-O-acetyl-3,4,6-tri-O-benzyl-alpha/beta-d-mannopyranosyl trichloroacetimidate to yield alpha-Manp-(1-->2) oligomers. A starch-derived trimer was also synthesized as a control. To promote hydration and form stable archaeosomes, an archaeal anionic lipid archaetidylglycerol (AG) was included in a 4:1 molar ratio. Archaeosomes prepared from Manp(1-2)-AG were recovered at only 34-37%, whereas Manp(3-4)-AG recoveries were 72-77%. Lipid recovery following hydration of Manp(5)-AG archaeosomes declined to 34%, indicating an optimum of 3-4 Manp units for bilayer formation. The CD8(+) T cell response in mice immunized with Manp(3-5) archaeosomes containing ovalbumin was highest for Manp(4) and declined for Manp(3) and Manp(5), revealing an optimum length of four unbranched units. The starch-derived trimer was more active than the Manp oligomers, suggesting the involvement of either a general binding lectin on antigen-presenting cells with highest affinity for triglucose or multiple lectin receptors
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AffiliationNRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedNo
NPARC number9371079
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Record identifiereba43f7c-f26a-480a-9500-995b4b71f873
Record created2009-07-10
Record modified2016-05-09
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