Skip to main content

Research Repository

Advanced Search

New AMD3100 derivatives for CXCR4 chemokine receptor targeted molecular imaging studies: synthesis, anti-HIV-1 evaluation and binding affinities

Poty, Sophie; De?soge?re, Pauline; Goze, Christine; Boschetti, Frédéric; D‘huys, Thomas; Schols, Dominique; Cawthorne, Christopher; Archibald, Stephen J.; Maëcke, Helmut R.; Denat, Franck

Authors

Sophie Poty

Pauline De?soge?re

Christine Goze

Frédéric Boschetti

Thomas D‘huys

Dominique Schols

Christopher Cawthorne

Helmut R. Maëcke

Franck Denat



Abstract

CXCR4 is a target of growing interest for the development of new therapeutic drugs and imaging agents as its role in multiple disease states has been demonstrated. AMD3100, a CXCR4 chemokine receptor antagonist that is in current clinical use as a haematopoietic stem cell mobilising drug, has been widely studied for its anti-HIV properties, potential to inhibit metastatic spread of certain cancers and, more recently, its ability to chelate radiometals for nuclear imaging. In this study, AMD3100 is functionalised on the phenyl moiety to investigate the influence of the structural modification on the anti-HIV-1 properties and receptor affinity in competition with anti-CXCR4 monoclonal antibodies and the natural ligand for CXCR4, CXCL12. The effect of complexation of nickel(II) in the cyclam cavities has been investigated. Two amino derivatives were obtained and are suitable intermediates for conjugation reactions to obtain CXCR4 molecular imaging agents. A fluorescent probe (BODIPY) and a precursor for 18F (positron emitting isotope) radiolabelling were conjugated to validate this route to new CXCR4 imaging agents.

Citation

Poty, S., Désogère, P., Goze, C., Boschetti, F., D‘huys, T., Schols, D., …Denat, F. (2015). New AMD3100 derivatives for CXCR4 chemokine receptor targeted molecular imaging studies: synthesis, anti-HIV-1 evaluation and binding affinities. Dalton Transactions : an international journal of inorganic chemistry, 44(11), 5004-5016. https://doi.org/10.1039/c4dt02972k

Journal Article Type Article
Acceptance Date Jan 20, 2015
Online Publication Date Jan 20, 2015
Publication Date Mar 21, 2015
Deposit Date May 19, 2016
Publicly Available Date Mar 28, 2024
Journal Dalton transactions
Print ISSN 1477-9226
Electronic ISSN 1477-9234
Publisher Royal Society of Chemistry
Peer Reviewed Peer Reviewed
Volume 44
Issue 11
Pages 5004-5016
DOI https://doi.org/10.1039/c4dt02972k
Keywords CXCR4
Public URL https://hull-repository.worktribe.com/output/438374
Publisher URL http://pubs.rsc.org/en/Content/ArticleLanding/2015/DT/C4DT02972K#!divAbstract
Additional Information This is an authors accepted manuscript of an article published in Dalton transactions, 2015, v.44.

Files






You might also like



Downloadable Citations