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Ligand Induced Cu II Transport Restricts Cancer and Mycobacterial Growth: Towards a Plug‐and‐Select Ion Channel Scaffold
Author(s) -
Saha Parichita,
Kumari Agarwala Prema,
Dadhich Ruchika,
Adhyapak Pranav,
Kapoor Shobhna,
Madhavan Nandita
Publication year - 2021
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202000731
Subject(s) - tripeptide , ion channel , antiporter , ligand (biochemistry) , chemistry , selectivity , peptide , divalent , biophysics , combinatorial chemistry , ion transporter , membrane , cancer cell , scaffold , biochemistry , biology , cancer , receptor , organic chemistry , genetics , catalysis , medicine , biomedical engineering
Synthetic channels with high ion selectivity are attractive drug targets for diseases involving ion dysregulation. Achieving selective transport of divalent ions is highly challenging due their high hydration energies. A small tripeptide amphiphilic scaffold installed with a pybox ligand selectively transports Cu II ions across membranes. The peptide forms stable dimeric pores in the membrane and transports ions by a Cu 2+ /H + antiport mechanism. The ligand‐induced excellent Cu II selectivity as well as high membrane permeability of the peptide is exploited to promote cancer cell death. The peptide's ability to restrict mycobacterial growth serves as seeds to evolve antibacterial strategies centred on selectively modulating ion homeostasis in pathogens. This simple peptide can potentially function as a universal, yet versatile, scaffold wherein the ion selectivity can be precisely controlled by modifying the ligand at the C terminus.