Reversible Photocontrol of Peptide Conformation with a Rhodopsin like Photoswitch Marina Blanco-Lomas,†,§ Subhas Samanta,‡,§ Pedro J. Campos,† G. Andrew Woolley,*,‡ and Diego Sampedro*,† †Departamento de Química, Unidad Asociada al C.S.I.C., Universidad de La Rioja, Madre de Dios 51, E-26006 Logroño, La Rioja, Spain ‡Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, Canada M5S 3H6

Protonated retinal schiff base chromophore of rhodopsin- Photoswitch shaped by nature.

Fig. S0. UV-Vis spectra of the pure E isomer of (2) in acetonitrile, the PSS obtained with 313 nm irradiation (60/40 Z/E, determined by NMR) and the calculated spectrum of the pure Z isomer.

E to Z isomerization quantum yield of 1 Figure 1. (a) UV−vis spectra of the SS-11 peptide cross-linked with 2 in the dark-adapted E form in aqueous solution at different pHs (as indicated) at 20 °C. (b) Photoisomerization of the SS-11 peptide cross-linked with 2 at pH 5.0. Spectra of the pure E and Z forms of the cross-linked peptide (isolated by HPLC) are shown. Photostationary states (PSSs) at 400 and 446 nm are 7/93 E/Z and 78/22 E/Z, respectively. E to Z isomerization quantum yield of 1 Unprotonated in acetonitrile- 0.6 Protonated chromophore attached to a peptide in water- 0.24

Figure 2. Multiple rounds of photoswitching of the SS-11 peptide cross-linked using 2 with alternating violet (400 nm) and blue (446 nm) light in aqueous solution at 20 °C.

Fig. S5 Thermal relaxation of the Z-form of (2)-cross-linked SS-11 after exposure to 400 nm light in 20 mM sodium phosphate buffer, pH 5.0.

Figure 3. (a) Calculated change in the end-to-end distance between S atom attachment points for the E and Z forms of the photoswitch

(b) CD spectra of the peptide SS-11

(d) Illustration of the cross-linked peptide with the photoswitch in the helix-stabilizing E form. (e) Illustration showing disruption of the helical structure by the Z form of the photoswitch.

Conclusion Effective photocontrol of peptide conformation in aqueous environment using visible wavelengths, slow thermal relaxation, efficiency in photoswiching etc make the present rhodopsin like photoswitch an attractive candidate for peptide and protein photocontrol, that can have application in wide variety of targets.