Optical Control of Cytokine Production Using Photoswitchable Galactosylceramides. Issue 20 (9th March 2020)

• Record Type: Journal Article
• Authors: Hartrampf, Nina; Seki, Toshiyuki; Baumann, Andreas; Watson, Philip; Vepřek, Nynke A.; Hetzler, Belinda E.; Hoffmann‐Röder, Anja; Tsuji, Moriya; Trauner, Dirk
• Is Part Of: Chemistry. Volume 26:Issue 20(2020)
• Page Start: 4476
• Page End: 4479
• Publication Date: 2020-03-09
• Subjects: azobenzenes -- cancer immunotherapy -- galactosyl ceramides -- natural killer T cells -- photopharmacology; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201905279
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: α‐Galactosylceramides are glycosphingolipids that show promise in cancer immunotherapy. After presentation by CD1d, they activate natural killer T cells (NKT), which results in the production of a variety of pro‐inflammatory and immunomodulatory cytokines. Herein, we report the synthesis and biological evaluation of photochromic derivatives of KRN‐7000, the activity of which can be modulated with light. Based on established structure–activity relationships, we designed photoswitchable analogues of this glycolipid that control the production of pro‐inflammatory cytokines, such as IFN‐γ. The azobenzene derivative α‐GalACer‐4 proved to be more potent than KRN‐7000 itself when activated with 370 nm light. Photolipids of this type could improve our mechanistic understanding of cytokine production and could open new directions in photoimmunotherapy. Abstract : A new direction in photoimmunotherapy : The synthesis and biological evaluation of photochromic derivatives of the α‐galactosylceramide KRN‐7000 are reported. The photolipid α‐GalACer‐4 proved to be more potent than KRN‐7000 itself when activated with 370 nm light (see scheme).