Identification of selective neuropeptide Y2 peptide agonists

Lynn B DeCarr; Thomas M Buckholz; Philip D G Coish; Zahra Fathi; Stephen E Fisk; Michelle R Mays; Stephen J O'Connor; Kevin J Lumb

doi:10.1016/j.bmcl.2006.10.007

Identification of selective neuropeptide Y2 peptide agonists

Bioorg Med Chem Lett. 2007 Jan 15;17(2):538-41. doi: 10.1016/j.bmcl.2006.10.007. Epub 2006 Oct 7.

Authors

Lynn B DeCarr¹, Thomas M Buckholz, Philip D G Coish, Zahra Fathi, Stephen E Fisk, Michelle R Mays, Stephen J O'Connor, Kevin J Lumb

Affiliation

¹ Department of Metabolic Disorders Research, Bayer Pharmaceuticals Corporation, 400 Morgan Lane, West Haven, CT 06516, USA.

PMID: 17055726
DOI: 10.1016/j.bmcl.2006.10.007

Abstract

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.

MeSH terms

Binding, Competitive / drug effects
Cell Line
Chromatography, High Pressure Liquid
Eating / drug effects*
Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
Humans
Indicators and Reagents
Peptide Fragments
Peptide YY / chemistry*
Peptide YY / pharmacology*
Receptors, Neuropeptide Y / agonists*
Receptors, Neuropeptide Y / drug effects

Substances

Indicators and Reagents
Peptide Fragments
Receptors, Neuropeptide Y
neuropeptide Y-Y1 receptor
neuropeptide Y2 receptor
neuropeptide Y5 receptor
Peptide YY
peptide YY (3-36)
Guanosine 5'-O-(3-Thiotriphosphate)