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Issue 35, 2018
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Synthesis and biological activity of a CXCR4-targeting bis(cyclam) lipid

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Abstract

A bis(cyclam)-capped cholesterol lipid designed to bind C–X–C chemokine receptor type 4 (CXCR4) was synthesised in good overall yield from 4-methoxyphenol through a seven step synthetic route, which also provided a bis(cyclam) intermediate bearing an octaethyleneglycol-primary amine that can be easily derivatised. This bis(cyclam)-capped cholesterol lipid was water soluble and self-assembled into micellar and non-micellar aggregates in water at concentrations above 8 μM. The bioactivity of the bis(cyclam)-capped cholesterol lipid was assessed using primary chronic lymphocytic leukaemia (CLL) cells, first with a competition binding assay then with a chemotaxis assay along a C–X–C motif chemokine ligand 12 (CXCL12) concentration gradient. At 20 μM, the bis(cyclam)-capped cholesterol lipid was as effective as the commercial drug AMD3100 for preventing the migration of CLL cells, despite a lower affinity for CXCR4 than AMD3100.

Graphical abstract: Synthesis and biological activity of a CXCR4-targeting bis(cyclam) lipid

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Publication details

The article was received on 18 Jun 2018, accepted on 17 Aug 2018 and first published on 20 Aug 2018


Article type: Paper
DOI: 10.1039/C8OB01439F
Citation: Org. Biomol. Chem., 2018,16, 6479-6490
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    Synthesis and biological activity of a CXCR4-targeting bis(cyclam) lipid

    A. D. Peters, C. McCallion, A. Booth, J. A. Adams, K. Rees-Unwin, A. Pluen, J. Burthem and S. J. Webb, Org. Biomol. Chem., 2018, 16, 6479
    DOI: 10.1039/C8OB01439F

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