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

Research output: Contribution to journalArticle

  • External authors:
  • Anna Peters
  • Catriona Mccallion
  • Andrew Booth
  • Julie A Adams
  • Karen Rees-Unwin


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.

Bibliographical metadata

Original languageEnglish
JournalOrganic and Biomolecular Chemistry
Early online date20 Aug 2018
Publication statusPublished - 2018

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