Identification of selective neuropeptide Y2 peptide agonists

• Published in: Bioorganic & medicinal chemistry letters 2007-01, Vol.17 (2), p.538-541
• Main Authors: DeCarr, Lynn B., Buckholz, Thomas M., Coish, Philip D.G., Fathi, Zahra, Fisk, Stephen E., Mays, Michelle R., O’Connor, Stephen J., Lumb, Kevin J.
• Format: Article
• Language: English
• Subjects: Binding, Competitive - drug effects; Biological and medical sciences; Cell Line; Chromatography, High Pressure Liquid; Eating - drug effects; General and cellular metabolism. Vitamins; Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology; Humans; Indicators and Reagents; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; NPY; NPY2; Obesity; Peptide; Peptide Fragments; Peptide YY - chemistry; Peptide YY - pharmacology; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; PYY; Receptors, Neuropeptide Y - agonists; Receptors, Neuropeptide Y - drug effects
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2006.10.007

A series of potent and selective NPY2 receptor agonist peptides are described. Activation of the NPY2 receptor to reduce appetite while avoiding stimulation of the NPY1 and NPY5 receptors that induce feeding provides a pharmaceutical approach to modulate food intake. The naturally occurring peptide PYY(3–36) is a nonselective NPY1, NPY2, and NPY5 agonist. N-terminal truncation of PYY to abrogate affinity for the NPY1 and NPY5 receptors and subsequent N-terminal modification with aminobenzoic analogs to restore NPY2 receptor potency results in a series of highly selective NPY2 receptor peptide agonists.