1.D.146.  The Halogen-bond-mediated Artificial Chloride Channel (HACC) Family

Chloride-selective transmembrane carriers and channels have uses in treating channelopathies and cancers. Most reported artificial channel systems lack clearly definable and readily modifiable positions in their structures for the reliable construction and combinatorial optimization of their ion transport properties. Most of these existing channels are limited by their large molecular weights, weak activities or low anion selectivities.  Ren et al. 2018 described a readily accessible and robust monopeptide-based scaffold for the reliable construction of halogen bond-mediated artificial anion channels via directional assembly of electron-deficient iodine atoms, which create a transmembrane pathway for facilitating anion transport. The high intrinsic modularity of the backbone of the scaffold, which enables the rapid and combinatorial optimization of the transport activity and selectivity of channels, effectively delivers a highly active chloride channel (e.g., A10, L8 and L10). Such high activity in chloride transport subsequently leads to an excellent IC50 value of 20 μM toward inhibiting the growth of human breast cancer cells (BT-474), an anticancer activity that is even higher than that of the well-known anticancer agent cisplatin (Ren et al. 2018).



Ren, C., X. Ding, A. Roy, J. Shen, S. Zhou, F. Chen, S.F. Yau Li, H. Ren, Y.Y. Yang, and H. Zeng. (2018). A halogen bond-mediated highly active artificial chloride channel with high anticancer activity. Chem Sci 9: 4044-4051.