Augmented photoswitching modulates immune signaling.
Reversible and non-invasive photoswitching of the immunosuppressive effect of a drug would be a very valuable tool for precisely regulating the immune system. Using a combination of protein borrowing and two-photon photoisomerization, we designed and synthesized derivatives of cyclosporin A. Here we demonstrate photoswitching of the local conformation within small molecules, which we used to modulate inhibitory potencies for cyclophilin, influence ternary and quaternary complex formations and regulate T-cell transcriptional activation in situ.
Zhang
Yixin
Y
Max Planck Research Unit for Enzymology of Protein Folding, Halle, Germany.
Erdmann
Frank
F
Fischer
Gunter
G
D001391:Azo Compounds / Q000737:chemistry; D002478:Cells, Cultured; D021983:Cyclophilins / Q000037:antagonists & inhibitors*; D016572:Cyclosporine / Q000737:chemistry* / Q000494:pharmacology* / Q000528:radiation effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000528:radiation effects; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000528:radiation effects; D008027:Light; D015394:Molecular Structure; D011485:Protein Binding; D013237:Stereoisomerism; D019809:Streptavidin / Q000737:chemistry; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000528:radiation effects
D001391:Azo Compounds; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D016572:Cyclosporine; D019809:Streptavidin; D021983:Cyclophilins; C009850:azobenzene