Rational design of conformationally constrained cyclopentapeptide antagonists for C-x-C chemokine receptor 4 (CXCR4)

Jignesh Mungalpara; Stefanie Thiele; Øystein Eriksen; Johann Eksteen; Mette M Rosenkilde; Jon Våbenø

doi:10.1021/jm300926y

Rational design of conformationally constrained cyclopentapeptide antagonists for C-x-C chemokine receptor 4 (CXCR4)

Jignesh Mungalpara, Stefanie Thiele, Øystein Eriksen, Johann Eksteen, Mette M Rosenkilde, Jon Våbenø

25 Citations (Scopus)

Abstract

In the absence of an experimentally determined binding mode for the cyclopentapeptide CXCR4 antagonists, we have rationally designed conformationally constrained analogues to further probe the small peptide binding pocket of CXCR4. Two different rigidification strategies were employed, both resulting in highly potent ligands (9 and 13). The information provided by this cyclopentapeptide ligand series will be very valuable in the development of novel peptidomimetic CXCR4 antagonists.

Original language	English
Journal	Journal of Medicinal Chemistry
Volume	55
Issue number	22
Pages (from-to)	10287-10291
Number of pages	5
ISSN	0022-2623
DOIs	https://doi.org/10.1021/jm300926y
Publication status	Published - 26 Nov 2012

Keywords

Drug Design
Humans
Ligands
Models, Molecular
Molecular Conformation
Peptides, Cyclic
Peptidomimetics
Protein Conformation
Receptors, CXCR4

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10.1021/jm300926y

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title = "Rational design of conformationally constrained cyclopentapeptide antagonists for C-x-C chemokine receptor 4 (CXCR4)",

abstract = "In the absence of an experimentally determined binding mode for the cyclopentapeptide CXCR4 antagonists, we have rationally designed conformationally constrained analogues to further probe the small peptide binding pocket of CXCR4. Two different rigidification strategies were employed, both resulting in highly potent ligands (9 and 13). The information provided by this cyclopentapeptide ligand series will be very valuable in the development of novel peptidomimetic CXCR4 antagonists.",

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author = "Jignesh Mungalpara and Stefanie Thiele and {\O}ystein Eriksen and Johann Eksteen and Rosenkilde, {Mette M} and Jon V{\aa}ben{\o}",

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T1 - Rational design of conformationally constrained cyclopentapeptide antagonists for C-x-C chemokine receptor 4 (CXCR4)

AU - Mungalpara, Jignesh

AU - Thiele, Stefanie

AU - Eriksen, Øystein

AU - Eksteen, Johann

AU - Rosenkilde, Mette M

AU - Våbenø, Jon

PY - 2012/11/26

Y1 - 2012/11/26

N2 - In the absence of an experimentally determined binding mode for the cyclopentapeptide CXCR4 antagonists, we have rationally designed conformationally constrained analogues to further probe the small peptide binding pocket of CXCR4. Two different rigidification strategies were employed, both resulting in highly potent ligands (9 and 13). The information provided by this cyclopentapeptide ligand series will be very valuable in the development of novel peptidomimetic CXCR4 antagonists.

AB - In the absence of an experimentally determined binding mode for the cyclopentapeptide CXCR4 antagonists, we have rationally designed conformationally constrained analogues to further probe the small peptide binding pocket of CXCR4. Two different rigidification strategies were employed, both resulting in highly potent ligands (9 and 13). The information provided by this cyclopentapeptide ligand series will be very valuable in the development of novel peptidomimetic CXCR4 antagonists.

KW - Drug Design

KW - Humans

KW - Ligands

KW - Models, Molecular

KW - Molecular Conformation

KW - Peptides, Cyclic

KW - Peptidomimetics

KW - Protein Conformation

KW - Receptors, CXCR4

U2 - 10.1021/jm300926y

DO - 10.1021/jm300926y

M3 - Journal article

C2 - 23043442

SN - 0022-2623

VL - 55

SP - 10287

EP - 10291

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 22

ER -

Rational design of conformationally constrained cyclopentapeptide antagonists for C-x-C chemokine receptor 4 (CXCR4)

Abstract

Keywords

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