title: Synthesis and Activity of 6″-Deoxy-6″-thio-α-GalCer and Peptide Conjugates.
abstract: A major challenge in the development of highly defined synthetic vaccines is the codelivery of vaccine components (i.e., antigen and adjuvant) to secondary lymphoid tissue to induce optimal immune responses. This problem can be addressed by synthesizing vaccines that comprise peptide antigens covalently attached to glycolipid adjuvants through biologically cleavable linkers. Toward this, a strategy utilizing previously unreported 6″-deoxy-6″-thio analogues of α-GalCer that can undergo chemoselective conjugation with peptide antigens is described. Administration of these conjugate vaccines leads to enhanced priming of antigen specific T cells. This simple vaccine design is broadly applicable to multiple disease indications such as cancer and infectious disease.
authors.affiliation: The Ferrier Research Institute, Victoria University of Wellington , P.O. Box 600, Wellington 6140, New Zealand.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Compton
authors.affiliation: Malaghan Institute of Medical Research , P.O. Box 7060, Wellington 6242, New Zealand.
authors.forename: Ching-wen
authors.initials: CW
authors.lastname: Tang
authors.affiliation: The Ferrier Research Institute, Victoria University of Wellington , P.O. Box 600, Wellington 6140, New Zealand.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Johnston
authors.affiliation: Malaghan Institute of Medical Research , P.O. Box 7060, Wellington 6242, New Zealand.
authors.forename: Taryn L
authors.initials: TL
authors.lastname: Osmond
authors.affiliation: The Ferrier Research Institute, Victoria University of Wellington , P.O. Box 600, Wellington 6140, New Zealand.
authors.forename: Colin M
authors.initials: CM
authors.lastname: Hayman
authors.affiliation: Department of Chemistry, University of Otago , P.O. Box 56, Dunedin 9054, New Zealand.
authors.forename: David S
authors.initials: DS
authors.lastname: Larsen
authors.affiliation: Malaghan Institute of Medical Research , P.O. Box 7060, Wellington 6242, New Zealand.|School of Biological Sciences, Victoria University of Wellington , P.O. Box 600, Wellington 6140, New Zealand.|Maurice Wilkins Centre for Molecular Biodiscovery , 3 Symonds Street, Auckland Central 1142, New Zealand.
authors.forename: Ian F
authors.initials: IF
authors.lastname: Hermans
authors.affiliation: The Ferrier Research Institute, Victoria University of Wellington , P.O. Box 600, Wellington 6140, New Zealand.|Maurice Wilkins Centre for Molecular Biodiscovery , 3 Symonds Street, Auckland Central 1142, New Zealand.
authors.forename: Gavin F
authors.initials: GF
authors.lastname: Painter
mesh_terms: D002586:Cesium / Q000032:analysis; D005699:Galactosylceramides / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D047028:Macrocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D008301:Maleimides / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D005699:Galactosylceramides; D047028:Macrocyclic Compounds; D008301:Maleimides; D010455:Peptides; C493154:alpha-galactosylceramide; D002586:Cesium