Neuropeptide Y (NPY) is a peptidic neurotransmitter abundantly expressed in human physiological systems. It elicits many physiological and pathophysiological functions by activating Y receptors. Our work has applied a variety of synthetic approaches to develop peptide conjugates that possess affinity to the Y1 and Y4 receptor subtypes. These conjugates may offer great potential for studying fundamental features of Y receptor localisation, functions and leading therapeutic targeting.
Using modern peptide synthesis and conjugation strategies, we have identified two groups of fluorescently labelled peptide conjugates originated from the C-terminal fragment of NPY. The first group contains peptides derived from the monomeric BVD-15 peptide scaffold that show strong Y1 receptor affinity. The second group includes peptides derived from the dimeric, dicarba-bridged BVD-74D scaffold that have potent activity at Y4 receptors. These ligands show a range of properties such as single and dual subtype selectivity, agonism and antagonism – that allow them to be used as pharmacological tools for studying Y receptors.