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

ABSTRACT: 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 ?(CONH) bonds at positions 30-31 and 33-34 are particularly important for receptor interaction and that the latter is implicated in Y2 receptor selectivity.

SUBMITTER: Albertsen L

PROVIDER: S-EPMC4027376 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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

Albertsen Louise L Andersen Julie J JJ Paulsson Johan F JF Thomsen Jens K JK Norrild Jens C JC Strømgaard Kristian K

ACS medicinal chemistry letters 20131021 12

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 ...[more]

PMID: 24900634

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