title: Synthesis of C6''-modified α-C-GalCer analogues as mouse and human iNKT cell agonists.
abstract: α-GalCer analogues that combine known Th1 polarizing C6''-modifications with a C-glycosidic linkage were synthesized. We employed a protecting group strategy that allowed the preparation of both saturated and unsaturated derivatives with variable C6''-substituents. Selected analogues demonstrate promising activity in mice. Interestingly, the introduction of a 6''-O-pyridinylcarbamoyl substituent to α-C-GalCer restores its antigenicity in human iNKT cells.
authors.affiliation: Laboratory for Medicinal Chemistry (FFW), Faculty of Pharmaceutical Sciences, UGent, Ottergemsesteenweg 460, B-9000 Ghent, Belgium. serge.vancalenbergh@ugent.be.
authors.forename: Joren
authors.initials: J
authors.lastname: Guillaume
authors.affiliation: Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, New York, USA.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Seki
authors.affiliation: Department of Internal Medicine, Faculty of Medicine and Health Sciences, Ghent University, B-9000 Ghent, Belgium and VIB Inflammation Research Center, Ghent University, Ghent, Belgium.
authors.forename: Tine
authors.initials: T
authors.lastname: Decruy
authors.affiliation: Department of Internal Medicine, Faculty of Medicine and Health Sciences, Ghent University, B-9000 Ghent, Belgium and VIB Inflammation Research Center, Ghent University, Ghent, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Venken
authors.affiliation: Department of Internal Medicine, Faculty of Medicine and Health Sciences, Ghent University, B-9000 Ghent, Belgium and VIB Inflammation Research Center, Ghent University, Ghent, Belgium.
authors.forename: Dirk
authors.initials: D
authors.lastname: Elewaut
authors.affiliation: Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, New York, USA.
authors.forename: Moriya
authors.initials: M
authors.lastname: Tsuji
authors.affiliation: Laboratory for Medicinal Chemistry (FFW), Faculty of Pharmaceutical Sciences, UGent, Ottergemsesteenweg 460, B-9000 Ghent, Belgium. serge.vancalenbergh@ugent.be.
authors.forename: Serge
authors.identifier: http://orcid.org/0000-0002-4201-1264
authors.initials: S
authors.lastname: Van Calenbergh
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005699:Galactosylceramides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D055611:Natural Killer T-Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C550181:C-galactosylceramide; D016207:Cytokines; D005699:Galactosylceramides