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

Louise Albertsen; J.J. Andersen; J.F. Paulsson; J.K. Thomsen; Jens Chr. Norrild; K. Strømgaard

doi:10.1021/ml400335g

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

Louise Albertsen, J.J. Andersen, J.F. Paulsson, J.K. Thomsen, Jens Chr. Norrild, K. Strømgaard

5 Citationer (Scopus)

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 ψ(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.

Originalsprog	Engelsk
Tidsskrift	A C S Medicinal Chemistry Letters
Vol/bind	4
Udgave nummer	12
Sider (fra-til)	1228-1232
Antal sider	5
ISSN	1948-5875
DOI	https://doi.org/10.1021/ml400335g
Status	Udgivet - 12 dec. 2013

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title = "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 ψ(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.",

author = "Louise Albertsen and J.J. Andersen and J.F. Paulsson and J.K. Thomsen and Norrild, {Jens Chr.} and K. Str{\o}mgaard",

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T1 - Design and synthesis of peptide YY analogues with c-terminal backbone amide-to-ester modifications

AU - Albertsen, Louise

AU - Andersen, J.J.

AU - Paulsson, J.F.

AU - Thomsen, J.K.

AU - Norrild, Jens Chr.

AU - Strømgaard, K.

PY - 2013/12/12

Y1 - 2013/12/12

N2 - 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 Y2 receptor selectivity.

AB - 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 Y2 receptor selectivity.

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DO - 10.1021/ml400335g

M3 - Journal article

AN - SCOPUS:84890450993

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JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

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

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