Selective binding of Cu 2 + in water medium by a synthetic chelatori sapromising therapeutic approacht owards 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 ap rotein are hardly reported. Herein we describe the design and synthesis of an acetylatedp eptoid-N-substituted glycine trimer-that incorporates ap icolyl group at the N-terminal, an on-coordinating but structurally directing bulky chiral phenylethyl group at the C-terminus and am odified 2,2'-bipyridine group (PCA-Nspe), which selectively binds Cu 2 + to form aw ater-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 excesso fo ther biologically relevant metal ions such as Zn 2 + ,C o 2 + ,M n 2 + ,C a 2 + ,M g 2 + ,K + and Na + .B ased on spectroscopic data and DFT calculations of PCA-Nspe as well as of ac ontrol peptoid having an achiral benzylg roup instead of the phenylethyls ide chain, we could suggest that the chiral and bulkierp henylethyl group at the C-terminus controlst he preorganization of the two ligands, and this might play arole in the selectivity of PCA-Nspe.Significantly, we show that PCA-Nspe can extract Cu 2 + from the natural copperbinding protein metallothionein. Scheme1.Acartoonrepresentation of Cu 2 + chelation from ac opper storage protein by as uitable chelator:apossible remedyf or Wilsond isease and cancer.