A long-acting selective neuropeptide Y2 receptor PEGylated peptide agonist reduces food intake in mice.
Activation of the NPY2 receptor to reduce appetite while avoiding activation of the NPY1 and NPY5 receptors that stimulate feeding provides a pharmaceutical approach to modulate food intake. The naturally occurring peptide and development candidate PYY(3-36) is a non-selective NPY1, NPY2, and NPY5 agonist of limited in vivo duration of action. N-terminal modification with 20 kDa PEG of a selective NPY2 receptor agonist peptide results in a long-acting agent that outperforms PYY(3-36) in reducing food intake in mice. The results suggest that PEGylated, selective NPY2 peptide agonists offer a significantly improved therapeutic benefit over PYY(3-36) for obesity management.
DeCarr
Lynn B
LB
Department of Metabolic Disorders Research, Bayer Pharmaceuticals Corporation, 400 Morgan Lane, West Haven, CT 06516, USA.
Buckholz
Thomas M
TM
Milardo
Lucinda F
LF
Mays
Michelle R
MR
Ortiz
Astrid
A
Lumb
Kevin J
KJ
D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004435:Eating / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D051379:Mice; D008968:Molecular Conformation; D010446:Peptide Fragments; D019894:Peptide YY / Q000138:chemical synthesis* / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011485:Protein Binding; D017476:Receptors, Neuropeptide Y / Q000737:chemistry*
D010446:Peptide Fragments; D010455:Peptides; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D019894:Peptide YY; C061785:peptide YY (3-36); D011092:Polyethylene Glycols