Inhibition of rhodopsin regeneration by cyclohexyl derivatives

Twenty two compounds, bearing some structural similarity either to the ring-end or aldehyde-end of 11-cis-retinal, have been screened for their effectiveness in decreasing the rate of regeneration of rhodopsin in vitro from 11-cis retinal and bovine opsin. The results of these experiments indicate that only those compounds containing a ring and having at least two methyl groups at the 1,5-ring positions are capable of decreasing the rate of regeneration of rhodopsin. Short-chain aldehydes resembling the aldehyde-end of retinal did not affect the rate of pigment formation. There was no additive effect of combining a dimethylcyclohexyl inhibitor and a short chain aldehyde. The methyl groups at the 1,5-positions may play a special role in anchoring the retinal into the protein binding site. This hypothesis is supported by the failure of the ring demethylated analogue, 11-cis, 1,1,5-desmethyl-5,6-dihydroretinal, to form pigment under the same conditions with which good pigment yields are obtained with 11-cis 5,6-dihydroretinal.