Receptor-Bound Conformation of α-Peptide of Transducin (Gt) is not Stabilized by a “π-Cation” Interaction but by Constrained Lactam Bridges Between Residues

Introduction Light-induced activation of rhodopsin (R*) leads to its conformation change and the binding of transducin Gt. Synthetic Gtα (340-350) peptide has been demonstrated to stabilize R* as does Gt. The bound conformation of R*-bound Gtα (340-350) has been determined by TrNOE NMR measurements [1]. The adjacent disposition of the ε-amino group of Lys-341 toward the side-chain phenyl ring of Phe-350 suggests a possible π-cation interaction. To investigate this π-cation hypothesis, we measured the affinity with R* of a series of α-peptide analogs with different para-substituents on the Phe-350 phenyl ring. In order to further exploit the proximity between the side chains of Lys-341 and Phe-350, we also prepared α-peptide analogs with straightforward lactam bridges between the side chains at 341 and 350.