| Affiliation: | 1. Department of Chemistry, New York University, 100 Washington Square East, New York, NY, 10003 USA;2. The Aaron Diamond AIDS Research Center, Affiliate of the Rockefeller University, 455 First Avenue, 7th Floor, New York, NY, 10016 USA;3. Department of Chemistry, New York University, 100 Washington Square East, New York, NY, 10003 USA Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstrasse 5–13, 81377 München, Germany;4. Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstrasse 5–13, 81377 München, Germany |
| 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. |
