TY - JOUR
T1 - The role of methylation in the copper(
ii
) coordination properties of a His-containing decapeptide
AU - Hautier, Alexandre
AU - Carvalho, Tiago
AU - Valensin, Daniela
AU - Simaan, A. Jalila
AU - Faure, Bruno
AU - Mateus, Pedro
AU - Delgado, Rita
AU - Iranzo, Olga
PY - 2019/1/16
Y1 - 2019/1/16
N2 - 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 NMe -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 NMe -Asp)] 2+ , 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 NMe -Asp)] 2+ 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 NMe -Asp peptide.
AB - 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 NMe -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 NMe -Asp)] 2+ , 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 NMe -Asp)] 2+ 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 NMe -Asp peptide.
U2 - 10.1039/C8DT05037F
DO - 10.1039/C8DT05037F
M3 - Article
C2 - 30648708
VL - 48
SP - 1859
EP - 1870
JO - Dalton transactions (Cambridge, England : 2003)
JF - Dalton transactions (Cambridge, England : 2003)
SN - 1477-9234
IS - 5
ER -