Methyl Substituents at the 11 or 12 Position of Retinal Profoundly and Differentially Affect Photochemistry and Signalling Activity of Rhodopsin

Alpha‐retinals as Rhodopsin Chromophores—Preference for the 9‐Z Configuration and Partial Agonist Activity†

“…Usually this blockage can be reversed by subsequent incubation with the native 11‐ Z retinal ( e.g. 23,31) with simultaneous formation of rhodopsin. However, in the case of the 11‐ Z α‐retinal we did not observe significant formation of rhodopsin upon incubation with the 11‐ Z retinal after the formation of α‐rhodopsin had leveled.…”

“…It is commonly found as the 11-Z isomer (rhodopsin, k max = 498 nm), but occasionally (10) as the 9-Z isomer (isorhodopsin, k max = 485 nm) that has a lower quantum efficiency (0.27) but proceeds through the same photointermediate cascade. In order to investigate the ligand-receptor interactions responsible for spectral tuning, receptor activation or the photochemical properties, many studies have analyzed photoreceptor pigments generated with a large variety of retinal analogs (2,(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). This has provided a bonanza of information on binding pocket constraints, molecular aspects of the photocascade and agonistic properties of ligand derivatives.…”

Impacts of retinal polyene (de)methylation on the photoisomerization mechanism and photon energy storage of rhodopsin

“…These interactions induce torsional distortion of the chromophore polyene chain in the C10Á Á ÁC13 region, thus facilitating fast izomerization upon excitation. For example, the substitution of methyl with hydrogen at the C13 position results in reduced QY (between 0.44 16 and 0.47 9 ) and slower photoproduct formation time (400 fs) 25 as compared to native Rh (0.65 QY 3 and 200 fs 1,22 photoproduct formation time), supporting crystallographic 37 and NMR 30 findings that the 13-methyl group contributes to pre-twisting of the C11QC12 bond. As a result, many studies focused on the impact of the 9-and 13-methyl groups on the photoisomerization process and receptor activation by using photoreceptor pigments generated with 11-cis-9-demethyl-retinal (9-dm-Rh), 11-cis-13demethyl-retinal (13-dm-Rh), 11-cis-10-methyl-13-demethyl-retinal (10-m-13-dm-Rh), and 11-cis-10-methyl-retinal derivatives (10-m-Rh).…”

“…[8][9][10][11][12][13][14][15][16][17][18][19][20][21] Therefore, it comes as no surprise that much effort has been devoted to experimental [8][9][10][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] and theoretical [31][32][33][34][35] investigations of synthetic pigments. However, there is a tight coupling between the chromophore and the receptor to achieve optimum stability of inactive dark and active conformations of the visual photopigment.…”

“…8 Resonance Raman intensities indicate that steric hindrance lost in the 13-dm-Rh chromophore can be reconstructed by adding an extra methyl group at the C10 position, forming 10-m-13-dm-Rh. 16,29 In a recent study, Sovdat et al 38 demonstrated that methyl substitution at the C10 position in the retinal backbone of all-trans-9,13-dimethyl-RPSB in solution leads to the electronic excited-state dynamics of the same speed as in the protein pocket, possibly due to inductive effects. 10 The C13-methyl group does not have a significant effect on the absorption spectra of the pigment since the removal of a methyl group at the C13 position induces negligible changes in maximum absorption wavelength of both 13-dm-Rh and 10-m-13-dm-Rh with respect to the native pigment.…”