An N-terminally truncated PYY analogue, benzoyl-[Ala<sup>26</sup>,Ile<sup>28,31</sup>]PYY(25-36) (<b>1</b>), showed a relatively potent agonist activity for Y2R but a weak anorectic activity by intraperitoneal administration (2000 nmol/kg) in lean mice because of its markedly poor biological stability in the mouse serum.
A combination of the N-terminal 4-imidazolecarbonyl moiety and three amino acid substitutions, trans-4-hydroxy-d-proline (d-Hyp)<sup>24</sup>, isovaline (Iva)<sup>25</sup>, and γ-methylleucine (γMeLeu)<sup>28</sup>, not only improved the binding affinity of the peptide for Y2R but also increased its anorectic activity in lean mice.