N-Methylation of the peptide amide bond has proven to be a powerful strategy to fine-tune the conformation and properties of peptides. In this context and for the first time， we show that N-methylation can also be used to control the copper(ii) coordination properties of peptides and stabilize at high pH values the copper(ii) species lacking amidate coordination. Namely， we have prepared a derivative of the O-Asp peptide where the copper(ii) coordinating amino acids， i.e. Asp and His residues， were N-methylated (O-Asp). A combined study using potentiometric and spectroscopic (UV-Vis， CD， EPR and NMR) techniques indicates the formation of the wanted major species， [CuH(O-Asp)]， where copper(ii) i... More
N-Methylation of the peptide amide bond has proven to be a powerful strategy to fine-tune the conformation and properties of peptides. In this context and for the first time， we show that N-methylation can also be used to control the copper(ii) coordination properties of peptides and stabilize at high pH values the copper(ii) species lacking amidate coordination. Namely， we have prepared a derivative of the O-Asp peptide where the copper(ii) coordinating amino acids， i.e. Asp and His residues， were N-methylated (O-Asp). A combined study using potentiometric and spectroscopic (UV-Vis， CD， EPR and NMR) techniques indicates the formation of the wanted major species， [CuH(O-Asp)]， where copper(ii) is bound to His4(Nε)， His7(Nε)， His9(Nε) and Asp2(COO). With respect to the parent non-methylated O-Asp peptide， [CuH(O-Asp)] is stable at higher pH values but has lower affinity for copper(ii). Additionally， electrochemical studies reveal a Cu(ii) ⇌ Cu(i) redox process with a larger cathodic and anodic peak separation. Species containing copper(ii) coordinating amidates were not observed for this O-Asp peptide.
