Design and Synthesis of Peptide YY Analogues with C-terminal Backbone Amide-to-Ester Modifications

作者：Albertsen Louise; Andersen Julie J; Paulsson Johan F; Thomsen Jens K; Norrild Jens C; Stromgaard Kristian^*

来源：ACS Medicinal Chemistry Letters, 2013, 4(12): 1228-1232.

DOI：10.1021/ml400335g

• Peptide YY
• PYY
• amide-to-ester modifications
• neuropeptide Y
• NPY

Peptide YY (PYY) is a gut hormone that activates the G protein-coupled neuropeptide Y (NPY) receptors, and because of its appetite reducing actions, it is evaluated as an antiobesity drug candidate. The C-terminal tail of PYY is crucial for activation of the NPY receptors. Here, we describe the design and preparation of a series of PYY(3-36) depsipeptide analogues, in which backbone amide-to-ester modifications were systematically introduced in the C-terminal. Functional NPY receptor assays and circular dichroism revealed that the psi(CONH) bonds at positions 30-31 and 33-34 are particularly important for receptor interaction and that the latter is implicated in Y-2 receptor selectivity.

• 出版日期2013-12