Abstract
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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Liu, J. et al. Cell 66, 807–815 (1991).
Fischer, G. Angew. Chem. Int. Edn. Engl. 33, 1415–1436 (1994).
Jin, L. & Harrison, S.C. Proc. Natl. Acad. Sci. USA 99, 13522–13526 (2002).
Huai, Q. et al. Proc. Natl. Acad. Sci. USA 99, 12037–12042 (2002).
Behrendt, R. et al. Angew. Chem. Int. Edn. Engl. 38, 2771–2774 (1999).
Kumita, J.R., Smart, O.S. & Woolley, G.A. Proc. Natl. Acad. Sci. USA 97, 3803–3808 (2000).
Vollmer, M.S., Clark, T.D., Steinem, C. & Ghadiri, M.R. Angew. Chem. Int. Edn. Engl. 38, 1598–1601 (1999).
Westmark, P.R., Kelly, J.P. & Smith, B.D. J. Am. Chem. Soc. 115, 3416–3419 (1993).
Zhang, Y., Erdmann, F., Baumgrass, R., Schutkowski, M. & Fischer, G. J. Biol. Chem. 280, 4842–4850 (2005).
Churikov, V.M. et al. Opt. Commun. 209, 451–460 (2002).
Furuta, T. et al. Proc. Natl. Acad. Sci. USA 96, 1193–1200 (1999).
Cahalan, M.D., Parker, I., Wei, S.H. & Miller, M.J. Nat. Rev. Immunol. 2, 872–880 (2002).
Boulegue, C., Loweneck, M., Renner, C. & Moroder, L. Chem. Bio. Chem. 8, 591–594 (2007).
Baumgrass, R. et al. J. Biol. Chem. 279, 2470–2479 (2004).
Kullertz, G., Luthe, S. & Fischer, G. Clin. Chem. 44, 502–508 (1998).
Green, N.M. Methods Enzymol. 184, 51–67 (1990).
Fanghanel, J. & Fischer, G. Biophys. Chem. 100, 351–366 (2003).
Kiani, A., Rao, A. & Aramburu, J. Immunity 12, 359–372 (2000).
van Besouw, N.M. et al. Transplantation 70, 136–143 (2000).
van Besouw, N.M. et al. Transpl. Int. 9 (suppl. 1): S345–S347 (1996).
Briesewitz, R., Ray, G.T., Wandless, T.J. & Crabtree, G.R. Proc. Natl. Acad. Sci. USA 96, 1953–1958 (1999); comment in 96, 1826–1827 (1999).
Gestwicki, J.E., Crabtree, G.R. & Graef, I.A. Science 306, 865–869 (2004).
Liu, J.O. Chem. Biol. 6, R213–R215 (1999).
Fischer, G., Bang, H. & Mech, C. Biomed. Biochim. Acta 43, 1101–1111 (1984).
Waelkens, E., Goris, J., Di Salvo, J. & Merlevede, W. Biochem. Biophys. Res. Commun. 120, 397–404 (1984).
Acknowledgements
We thank the SFB610 of the Deutsche Forschungsgemeinschaft for supporting the work and M. Heidler and I. Kunze for their excellent technical assistance.
Author information
Authors and Affiliations
Contributions
Y.Z. and F.E. performed and analyzed experiments. Y.Z. synthesized all CsA derivatives and measured the enzymatic activities together with F.E. F.E. designed and performed all bioassays. G.F. prepared the manuscript and planned all experiments together with Y.Z. and F.E.
Corresponding author
Supplementary information
Supplementary Text and Figures
Supplementary Methods and Supplementary Results (PDF 2842 kb)
Rights and permissions
About this article
Cite this article
Zhang, Y., Erdmann, F. & Fischer, G. Augmented photoswitching modulates immune signaling. Nat Chem Biol 5, 724–726 (2009). https://doi.org/10.1038/nchembio.214
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nchembio.214
