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 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Journal of Medicinal Chemistry
Vol/bind	55
Udgave nummer	22
Sider (fra-til)	10287-10291
Antal sider	5
ISSN	0022-2623
DOI	https://doi.org/10.1021/jm300926y
Status	Udgivet - 26 nov. 2012

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10.1021/jm300926y

Citationsformater

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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.",

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

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

year = "2012",

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language = "English",

volume = "55",

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journal = "Journal of Medicinal Chemistry",

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TY - JOUR

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

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