Synthesis of CD3-Labeled 11-cis-Retinals and Application to Solid-State Deuterium NMR Spectroscopy of Rhodopsin

Efficient synthesis of 11-Z-retinals labeled with 2 H at the C5, C9, or C13 methyl groups is described. The 2 H-labeled retinals were used to regenerate the visual pigment rhodopsin for structural investigations. Solid-state 2 HNMR data provided the orientation of retinal within the rhodopsin binding pocket as well as its conformation. Extension of the approach to other membrane receptors can yield knowledge of their mechanisms of activation as a guide for ligand-based drug design.