2.B.106.  The PseudoPeptidic Cage-Chloride Carrier (PPC-ClC) Family 

Ignacio Alfonso and his group developed a pseudopeptidic cage (16) (see the Fig below) that shows pH-dependent chloride transport and also kills cancerous cells at acidic pH (Tapia et al. 2019).  The crystal structure of the peptide showed chloride binding via H-bonding interactions in the pocket. NMR titrations showed a strong 1 : 1 association (Ka ∼ 10-4 M−1) and a weak (approx. 10-2 M−1) 1 : 2 association of the cages with chloride ions. A structure with an –F substituent and a log P value of 4.31 was the most efficient chloride transporter, functioning by a carrier mechanism. The highest chloride transport rate was observed at pH 6.2 due to the enhanced chloride binding with the protonated tertiary amine.


(a) Structures of pseudopeptidic cages. (b) Mechanism of Cl− transport at pH 6.2 using pseudopeptidic cages 16c.

 

References:

Tapia, L., Y. Pérez, M. Bolte, J. Casas, J. Solà, R. Quesada, and I. Alfonso. (2019). pH-Dependent Chloride Transport by Pseudopeptidic Cages for the Selective Killing of Cancer Cells in Acidic Microenvironments. Angew Chem Int Ed Engl 58: 12465-12468.