Modeling Oxidative Damage of Peptides in the Gas Phase

摘要

Proteins are a major target for oxidative damage. Reactions with reactive oxygen species (ROS) such as ~(centre dot)OH lead to widespread and relatively non-specific damage. This typically occurs via initial hydrogen atom abstraction from either the alpha carbon on the peptide backbone, or suitable sites on the peptide side-chain. Under aerobic conditions the next step in the degradative process predominantly involves addition of O_(2). A complex cascade of reactions follow which may lead to cleavage of the peptide backbone or permanent modification of side-chains. Furthermore it has been demonstrated that a single ROS may lead to damage at multiple sites making elucidation of the mechanistic history impossible. Consequently studying these reactions in the solution phase can be difficult. In this study we have attempted to use the isolation, storage and activation capabilities of the ion-trap to examine individual steps relevent to oxidative damage. Specifically we have been concerned with the addition of molecular oxygen to peptide radicals. In addition we demonstrate that NO and NO_(2) may be utilized as probes of radical structure in the gas phase.