1.D.217. The Tetrafluoroiodobenzyl-decorated Monopeptide Scaffold (TFIB-MS-AT) Family
Ren et al. 2018 synthesised a monopeptide scaffold decorated with a tetrafluoroiodobenzyl group. These compounds had been shown to form 1D columnar stacks, and the authors envisioned this structure to self-assemble in a lipid bilayer providing a stabilizing path for anions through the polarized iodide atoms. The authors prepared a library of 15 compounds derived from five amino acids (alanine, phenylalanine, valine, leucine and isoleucine) and three alkyl chains of different lengths (8, 10 and 12 carbon atoms). A channel mechanism was characterised for 61L8 by single-channel current traces for chloride transport, recorded in a planar lipid bilayer at various voltages, and the activities of the compounds were quantified in model vesicles using the HPTS assay. The most active derivatives were 61A10, 61L8 and 61L10, with EC50 concentrations of 2.37, 0.39 and 0.93 μM, respectively. The calculated Hill coefficient was found to be above 3, supporting the need of cooperative action of several monomers to induce the transport activity. Derivative 61A10 was assayed in human breast cancer cells BT-474, and a concentration-dependent reduction of cell viability was observed with a calculated IC50 of 20 μM. This result represents an example of the usefulness of halogen bonds to produce biologically active anion carriers (Davis et al. 2020).