Molecular Recognition by a Short Partial Peptide of the Adrenergic Receptor: A Bottom-Up Approach

Receptor-neurotransmitter molecular recognition is key for neurotransmission. Although crystal structures of the receptors are known, the mechanism for recognition is not clear. Reported here is the ultraviolet (UV) and infrared (IR) spectra of complexes between a partial peptide (SIVSF), mimicking the binding motif of a catechol ring in the adrenergic receptor, and various ligands. The UV spectra show that two isomers coexist in the complex of SIVSF with properly recognized ligands, such as protonated adrenaline (adrenalineH⁺ ). From IR spectra, they are assigned to catechol- and amino-bound structures. The catechol-bound structure is not observed when the ligand is replaced by nonproper molecules, such as noradrenalineH⁺ . The results suggest that SIVSF not only recognizes the catechol ring but can distinguish differences in the amine side chain. The method provides a new possibility for screening molecules as potential therapeutics for activating the receptor.