Novel selective neuropeptide Y2 receptor PEGylated peptide agonists reduce food intake and body weight in mice.

Selective activation of the NPY2 receptor to suppress appetite provides an approach to obesity management. Selective NPY2 PEGylated peptide agonists are described that consist of a peptide core corresponding to residues 25-36 of PYY and a nonpeptidic moiety at the peptide N-terminus that contributes to in vitro potency and in vivo efficacy and provides a PEGylation site. The lead peptide elicits a dose-dependent reduction of food intake in lean mice and of food intake, body weight, and fat mass in DIO mice.