Amino acid influence on copper binding to peptides: cysteine versus arginine.

Matrix assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) and theoretical calculations [density functional theory (DFT)] were utilized to investigate the influence of cysteine side chain on Cu(+) binding to peptides and how Cu(+) ions competitively interact with cysteine (-SH/SO(3)H) versus arginine. Results from theoretical and experimental (fragmentation reactions) studies on [M + Cu](+) and [M + 2Cu - H](+) ions suggest that cysteine side chains (-SH) and cysteic acid (-SO(3)H) are important Cu(+) ligands. For example, we show that Cu(+) ions are competitively coordinated to the -SH or SO(3)H groups; however, we also present evidence that the proton of the SH/SO(3)H group is mobile and can be transferred to the arginine guanidine group. For [M + 2Cu - H](+) ions, deprotonation of the -SH/SO(3)H group is energetically more favorable than that of the carboxyl group, and the resulting thiolate/sulfonate group plays an important role in the coordination structure of [M + 2Cu - H](+) ions, as well as the fragmentation patterns. 2010 American Society for Mass Spectrometry. Published by Elsevier Inc. All rights reserved.