Synthesis of an hiv-1 related undecasaccharide containing an oligomannosidic heptasaccharide and a bacterial kdo-lipid a backbone

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Synthesis of an hiv-1 related undecasaccharide containing an oligomannosidic heptasaccharide and a bacterial kdo-lipid a backbone

Nino Trattnig 1 , Markus Blaukopf 1 , Ralph Pantophlet 2 , Paul Kosma 1

1 University of Natural Resources and Life Sciences, Vienna, Austria, 2 Faculty of Health Sciences, Burnaby, Canada

Gp120, present on the surface of the human immunodeficiency virus (HIV), harbors clusters of oligomannose structures that are recognized by several broadly neutralizing antibodies and thus constitutes an important target for HIV-1 vaccine development. Lipooligosaccharide (LOS), isolated from the bacterium Rhizobium radiobacter Rv3, closely resembles these oligomannose structures present on gp120 and immunization of wild-type mice with heat-killed bacteria elicited serum antibodies, which bound to monomeric gp120.[1] In order to boost the immune response against HIV-1 related oligomannosides we have set out to combine a recently identified broadly neutralizing heptamannosidic epitope with a common antigen of the inner core of bacterial lipopolysaccharide.[2]

Starting from the Kdo2GlcNAc2 tetrasaccharide 1, a central orthogonally mannose unit was coupled in good yield to OH-5 of the innermost Kdo residue,[3] which was followed by a blockwise coupling with an α-(1→2)-linked mannotriosyl trichloroacetimidate donor to introduce the D1-arm fragment. Deprotection of 3 led to the octasaccharide 5 corresponding to the R. radiobacter Rv3 lipooligosaccharide fragment. Next, glycosylation of O-6 of the inner mannose furnished 4 - harboring the D3-arm extension - followed by global deprotection to give the spacer-equipped undecasaccharide 6 featuring a hybrid structure of viral and bacterial epitopes.

Synthesis of rhizobial octasaccharide 5 and HIV-related undecasaccharide 6

Financial support from Austrian Science Fund (FWF, grant P26919-N28) and NIH (R01 AI134299 to RP).

Clark, B. E.; Auyeung, K.; Fregolino, E.; Parrilli, M.; Lanzetta, R.; De Castro, C.; Pantophlet, R. Chem. Biol. 2012, 19, 254.

Pantophlet, R.; Trattnig, N.; Murrell, S.; Lu, N.; Chau, D.; Rempel, C.; Wilson, I. A.; Kosma, P. Nat. Commun. 2017, 8, 1601.

Trattnig, N.; Farcet, J.-B.; Gritsch, P., Christler, A.; Pantophlet, R.; Kosma , P. J. Org. Chem. 2017, 82, 12346.

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