TY - JOUR
T1 - Optical Control of Cytokine Production Using Photoswitchable Galactosylceramides
AU - Hartrampf, Nina
AU - Seki, Toshiyuki
AU - Baumann, Andreas
AU - Watson, Philip
AU - Vepřek, Nynke A.
AU - Hetzler, Belinda E.
AU - Hoffmann-Röder, Anja
AU - Tsuji, Moriya
AU - Trauner, Dirk
N1 - Funding Information:
We acknowledge the Deutsche Telekom Foundation (Ph.D. fellowship to N.H.), the LMUMentoring program (fellowship N.H.), the German Academic Scholarship Foundation (Ph.D. Fellowship to N.A.V.), the New York University (MacCracken Fellowship to B.E.H.), as well as the Deutsche Forschungsgemeinschaft (SFB 749 and CIPSM) for generous funding. This work was partially supported by the National Institutes of Health Grant AI070258 (to M.T.).
Publisher Copyright:
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2020/4/6
Y1 - 2020/4/6
N2 - 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.
AB - 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.
KW - azobenzenes
KW - cancer immunotherapy
KW - galactosyl ceramides
KW - natural killer T cells
KW - photopharmacology
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U2 - 10.1002/chem.201905279
DO - 10.1002/chem.201905279
M3 - Article
C2 - 31788876
AN - SCOPUS:85081672741
SN - 0947-6539
VL - 26
SP - 4476
EP - 4479
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
IS - 20
ER -