Reactive Cu²⁺-peptide intermediates revealed by kinetic studies gain relevance by matching time windows in copper metallomics

The purpose of this essay is to propose that metallomic studies in the area of extracellular copper transport are incomplete without the explicit consideration of kinetics of Cu(2+)ion binding and exchange reactions. The kinetic data should be interpreted in the context of time constraints imposed by specific physiological processes. Examples from experimental studies of Cu2+ ion interactions with amino-terminal copper and nickel binding site/N-terminal site motifs are used to demonstrate that duration and periodicity of such processes as bloodstream transport or neurotransmission promote the reaction intermediates to the role of physiological effectors. The unexpectedly long lifetimes of intermediate complexes lead to their accumulation and novel reactivities. The emerging ideas are discussed in the context of other research areas in metallomics.