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A rationally designed peptoid for the selective chelation of Zn²⁺ over Cu².

ABSTRACT: The selective removal of Zn²⁺ from proteins by using a synthetic chelator is a promising therapeutic approach for the treatment of various diseases including cancer. Although the chelation of Zn²⁺ is well known, its removal from a protein in the presence of potential competing biologically relevant ions such as Cu²⁺ is hardly explored. Herein we present a peptoid - N-substituted glycine trimer - incorporating a picolyl group at the N-terminus, a non-coordinating but structurally directing benzyl group at the C-terminus and a 2,2':6',2''-terpyridine group in the second position, that selectively binds Zn²⁺ ions in the presence of excess Cu²⁺ ions in water. We further demonstrate that this chelator can selectively bind Zn²⁺ from a pool of excess biologically relevant and competitive ions (Cu²⁺, Fe³⁺, Ca²⁺, Mg²⁺, Na⁺, and K⁺) in a simulated body fluid (SBF), and also its ability to remove Zn²⁺ from a natural zinc protein domain (PYKCPECGKSFSQKSDLVKHQRTHTG) in a SBF.

SUBMITTER: Ghosh P

PROVIDER: S-EPMC8162371 | biostudies-literature |

REPOSITORIES: biostudies-literature

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