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A Water‐Soluble Peptoid that Can Extract Cu 2+ from Metallothionein via Selective Recognition
Author(s) -
Ghosh Pritam,
Maayan Galia
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202003711
Subject(s) - peptoid , chemistry , chelation , metallothionein , metal ions in aqueous solution , selectivity , stereochemistry , aqueous solution , combinatorial chemistry , metal , peptide , organic chemistry , biochemistry , zinc , catalysis
Selective binding of Cu 2+ in water medium by a synthetic chelator is a promising therapeutic approach towards the treatment of various diseases including cancer. Chelation of Cu 2+ is well exercised, however water‐soluble synthetic chelators that can selectively bind Cu 2+ from a pool of competing metal ions at very high excess and/or can extract Cu 2+ from a protein are hardly reported. Herein we describe the design and synthesis of an acetylated peptoid—N‐substituted glycine trimer—that incorporates a picolyl group at the N‐terminal, a non‐coordinating but structurally directing bulky chiral phenylethyl group at the C‐terminus and a modified 2,2′‐bipyridine group ( PCA‐Nspe ), which selectively binds Cu 2+ to form a water‐soluble complex. We further demonstrate that the selectivity of PCA‐Nspe to Cu 2+ is thermodynamically driven, leading to specific binding of Cu 2+ in an aqueous solution containing up to 60‐fold excess of other biologically relevant metal ions such as Zn 2+ , Co 2+ , Mn 2+ , Ca 2+ , Mg 2+ , K + and Na + . Based on spectroscopic data and DFT calculations of PCA‐Nspe as well as of a control peptoid having an achiral benzyl group instead of the phenylethyl side chain, we could suggest that the chiral and bulkier phenylethyl group at the C‐terminus controls the preorganization of the two ligands, and this might play a role in the selectivity of PCA‐Nspe . Significantly, we show that PCA‐Nspe can extract Cu 2+ from the natural copper binding protein metallothionein.