Combining elements from two antagonists of formyl peptide receptor 2  generates more potent peptidomimetic antagonists

Sarah Line Skovbakke; Andre Holdfeldt; Christina Nielsen; Anna Mette Hansen; Iris Perez-Gassol; Claes Dahlgren; Huamei Forsman; Henrik Franzyk

doi:10.1021/acs.jmedchem.7b00489

Combining elements from two antagonists of formyl peptide receptor 2 generates more potent peptidomimetic antagonists

Sarah Line Skovbakke, Andre Holdfeldt, Christina Nielsen, Anna Mette Hansen, Iris Perez-Gassol, Claes Dahlgren, Huamei Forsman, Henrik Franzyk

LUKKET: Institut for Lægemiddeldesign og Farmakologi

9 Citationer (Scopus)

Abstract

Structural optimization of a peptidomimetic antagonist of formyl peptide receptor 2 (FPR2) was explored by an approach involving combination of elements from the two most potent FPR2 antagonists described: a Rhodamine B-conjugated 10-residue gelsonin-derived peptide (i.e., PBP10, RhB-QRLFQVKGRR-OH) and the palmitoylated α-peptide/β-peptoid hybrid Pam-(Lys-βNspe)6-NH2. This generated an array of hybrid compounds from which a new subclass of receptor-selective antagonists was identified. The most potent representatives displayed activity in the low nanomolar range. The resulting stable and potent FPR2-selective antagonists (i.e., RhB-(Lys-βNphe)n-NH2; n = 4–6) are expected to become valuable tools in further elucidation of the physiological role of FPR2 in health and disease.

Originalsprog	Engelsk
Tidsskrift	Journal of Medicinal Chemistry
Vol/bind	60
Udgave nummer	16
Sider (fra-til)	6991-6997
ISSN	0022-2623
DOI	https://doi.org/10.1021/acs.jmedchem.7b00489
Status	Udgivet - 24 aug. 2017

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10.1021/acs.jmedchem.7b00489

Citationsformater

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title = "Combining elements from two antagonists of formyl peptide receptor 2 generates more potent peptidomimetic antagonists",

abstract = "Structural optimization of a peptidomimetic antagonist of formyl peptide receptor 2 (FPR2) was explored by an approach involving combination of elements from the two most potent FPR2 antagonists described: a Rhodamine B-conjugated 10-residue gelsonin-derived peptide (i.e., PBP10, RhB-QRLFQVKGRR-OH) and the palmitoylated α-peptide/β-peptoid hybrid Pam-(Lys-βNspe)6-NH2. This generated an array of hybrid compounds from which a new subclass of receptor-selective antagonists was identified. The most potent representatives displayed activity in the low nanomolar range. The resulting stable and potent FPR2-selective antagonists (i.e., RhB-(Lys-βNphe)n-NH2; n = 4–6) are expected to become valuable tools in further elucidation of the physiological role of FPR2 in health and disease.",

author = "Skovbakke, {Sarah Line} and Andre Holdfeldt and Christina Nielsen and Hansen, {Anna Mette} and Iris Perez-Gassol and Claes Dahlgren and Huamei Forsman and Henrik Franzyk",

year = "2017",

month = aug,

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doi = "10.1021/acs.jmedchem.7b00489",

language = "English",

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TY - JOUR

T1 - Combining elements from two antagonists of formyl peptide receptor 2 generates more potent peptidomimetic antagonists

AU - Skovbakke, Sarah Line

AU - Holdfeldt, Andre

AU - Nielsen, Christina

AU - Hansen, Anna Mette

AU - Perez-Gassol, Iris

AU - Dahlgren, Claes

AU - Forsman, Huamei

AU - Franzyk, Henrik

PY - 2017/8/24

Y1 - 2017/8/24

N2 - Structural optimization of a peptidomimetic antagonist of formyl peptide receptor 2 (FPR2) was explored by an approach involving combination of elements from the two most potent FPR2 antagonists described: a Rhodamine B-conjugated 10-residue gelsonin-derived peptide (i.e., PBP10, RhB-QRLFQVKGRR-OH) and the palmitoylated α-peptide/β-peptoid hybrid Pam-(Lys-βNspe)6-NH2. This generated an array of hybrid compounds from which a new subclass of receptor-selective antagonists was identified. The most potent representatives displayed activity in the low nanomolar range. The resulting stable and potent FPR2-selective antagonists (i.e., RhB-(Lys-βNphe)n-NH2; n = 4–6) are expected to become valuable tools in further elucidation of the physiological role of FPR2 in health and disease.

AB - Structural optimization of a peptidomimetic antagonist of formyl peptide receptor 2 (FPR2) was explored by an approach involving combination of elements from the two most potent FPR2 antagonists described: a Rhodamine B-conjugated 10-residue gelsonin-derived peptide (i.e., PBP10, RhB-QRLFQVKGRR-OH) and the palmitoylated α-peptide/β-peptoid hybrid Pam-(Lys-βNspe)6-NH2. This generated an array of hybrid compounds from which a new subclass of receptor-selective antagonists was identified. The most potent representatives displayed activity in the low nanomolar range. The resulting stable and potent FPR2-selective antagonists (i.e., RhB-(Lys-βNphe)n-NH2; n = 4–6) are expected to become valuable tools in further elucidation of the physiological role of FPR2 in health and disease.

U2 - 10.1021/acs.jmedchem.7b00489

DO - 10.1021/acs.jmedchem.7b00489

M3 - Journal article

C2 - 28700225

SN - 0022-2623

VL - 60

SP - 6991

EP - 6997

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 16

ER -

Combining elements from two antagonists of formyl peptide receptor 2 generates more potent peptidomimetic antagonists

Abstract

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