Design and evaluation of fluorescent and non-fluorescent bivalent ligands to explore their mode of action at neuropeptide Y receptors

This thesis describes the design and synthesis of novel fluorescent and non-fluorescent derivatives of the cyclic peptide GR231118 and the study of their actions at the Y1 and the Y4 receptors. A refined understanding of the molecular mechanism of peptide binding to the receptors was obtained. The effect of GR231118 treatment on receptor organisation at the cell membrane was also investigated. Results indicate that treatment with the dimer GR231118 peptide leads to Y1 receptor clustering. Collectively, the thesis improves understanding of the Y1 and Y4 receptor pharmacology which will lead the development of new therapeutic approaches in several diseases.