School of Life Science and Technology, Tokyo Institute of Technology, 4259 J2-10 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8501, Japan.
Department of Immunological Diagnosis, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 Japan.
Bioorg Med Chem Lett. 2020 Mar 1;30(5):126960. doi: 10.1016/j.bmcl.2020.126960. Epub 2020 Jan 11.
α-Galactosylceramide (α-GalCer) is recognized by the CD1d proteins on antigen-presenting cells at the ceramide moiety and the galactose moiety is presented to iNKT cells, which stimulates the immune responses. However, the immune suppression by repeated injections of α-GalCer has discouraged its development as an anti-cancer agent. To overcome the shortcoming by spatiotemporal restriction of its exposure, we synthesized the photochromic azobenzene-incorporated analogues and tested the photo-immunoregulation effect in its binding to CD1d. FACS analyses indicated that some of these analogues enhanced the affinity to CD1d on photo-irradiation by about 20%. A docking simulation suggests that the photochromic molecule should be bulkier for a clearer discrimination between on and off states.
α-半乳糖神经酰胺（α-GalCer）在抗原呈递细胞上的 CD1d 蛋白通过神经酰胺部分和半乳糖部分被识别，半乳糖部分被呈递给 iNKT 细胞，从而刺激免疫反应。然而，由于α-GalCer 的重复注射会产生免疫抑制作用，因此其作为抗癌药物的开发受到了阻碍。为了克服通过其暴露的时空限制来克服这一缺点，我们合成了光致变色的偶氮苯掺入类似物，并测试了其与 CD1d 结合的光免疫调节作用。FACS 分析表明，其中一些类似物通过光照射将与 CD1d 的亲和力提高了约 20%。对接模拟表明，光致变色分子应该更大，以便更清楚地区分开和关状态。
