Design and synthesis of peptide YY analogues with c-terminal backbone amide-to-ester modifications

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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 ψ(CONH) bonds at positions 30-31 and 33-34 are particularly important for receptor interaction and that the latter is implicated in Y receptor selectivity.
Original languageEnglish
JournalA C S Medicinal Chemistry Letters
Issue number12
Pages (from-to)1228-1232
Number of pages5
Publication statusPublished - 12 Dec 2013

ID: 96081753