Competitive Cu(II)-binding studies have been carried out between five decapeptides (both acyclic and cyclic), namely C-Asp, C-Asn, O-Asp, O-Dpro-Asp, and O-Asn, and the A beta(1-16) and A beta(1-40) fragments. Conformational constraints in such peptidic scaffolds affect their copper-binding affinity, which can be tuned. In the present study, the ability of these peptides to compete with A beta has been assessed in vitro, with the objective to examine whether such soft chelating agents may be used to lessen the deleterious interaction of Cu(II) with A beta. Fluorescence spectroscopy, electron paramagnetic resonance, and mass spectrometry data show that the more constrained peptide, i.e., cyclic C-Asp, which displays a Cu(II)-binding affinity comparable to that of A beta, is the only potential metal-protein attenuating compound (MPAC) candidate. In vitro aggregation studies with A beta(1-40) reveal that C-Asp can hamper the formation of copper-stabilized oligomeric A beta species, through capturing the metal ion prior to its interaction with monomeric A beta. The present study shows that (cyclic) peptides, preorganized for Cu(II) binding, may be applied for the development of potential copper-A beta attenuating compounds.