Identification of selective neuropeptide Y2 peptide agonists.
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.
DeCarr
Lynn B
LB
Department of Metabolic Disorders Research, Bayer Pharmaceuticals Corporation, 400 Morgan Lane, West Haven, CT 06516, USA.
Buckholz
Thomas M
TM
Coish
Philip D G
PD
Fathi
Zahra
Z
Fisk
Stephen E
SE
Mays
Michelle R
MR
O'Connor
Stephen J
SJ
Lumb
Kevin J
KJ
D001667:Binding, Competitive / Q000187:drug effects; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D004435:Eating / Q000187:drug effects*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D010446:Peptide Fragments; D019894:Peptide YY / Q000737:chemistry* / Q000494:pharmacology*; D017476:Receptors, Neuropeptide Y / Q000819:agonists* / Q000187:drug effects
D007202:Indicators and Reagents; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor; C100568:neuropeptide Y5 receptor; D019894:Peptide YY; C061785:peptide YY (3-36); D016244:Guanosine 5'-O-(3-Thiotriphosphate)