Re-evaluation of Cyclic Peptide Binding to Neurotensin Receptor 1 by Shifting the Peptide Register during Synthesis.

The head-to-tail cyclic peptide [Arg-Lys-Pro-Tyr-Tle-Leu] (peptide , where Tle is l--Leu) has previously been reported to bind to neurotensin receptor 1 (NTS1) (pKi = 5.97). Upon seeking to reproduce this finding, we found that peptide did not have a measurable affinity for NTS1.

Unravelling the mechanism of neurotensin recognition by neurotensin receptor 1.

The conformational ensembles of G protein-coupled receptors (GPCRs) include inactive and active states. Spectroscopy techniques, including NMR, show that agonists, antagonists and other ligands shift the ensemble toward specific states depending on the pharmacological efficacy of the ligand. How receptors recognize ligands and the kinetic mechanism underlying this population shift is poorly understood.