RESUMO
Amyloid beta (Aß) peptides and copper (Cu) ions are each involved in critical biological processes including antimicrobial activity, regulation of synaptic function, angiogenesis, and others. Aß binds to Cu and may play a role in Cu trafficking. Aß peptides exist in isoforms that vary at their C-and N-termini; variation at the N-terminal sequence affects Cu binding affinity, structure, and redox activity by providing different sets of coordinating groups to the metal ion. Several N-terminal isoforms have been detected in human brain tissues including Aß1-40/42, Aß3-42, pEAß3-42, Aß4-42, Aß11-40 and pEAß11-40 (where pE denotes an N-terminal pyroglutamic acid). Several previous works have individually investigated the affinity and structure of Cu(I) bound to some of these isoforms' metal binding domains. However, the disparately reported values are apparent constants collected under different sets of conditions, and thus an integrated comparison cannot be made. The work presented here provides the Cu(I) coordination structure and binding affinities of these six biologically relevant Aß isoforms determined in parallel using model peptides of the Aß metal binding domains (Aß1-16, Aß3-16, pEAß3-16, Aß4-16, Aß11-16 and pEAß11-16). The binding affinities of Cu(I)-Aß complexes were measured using solution competition with ferrozine (Fz) and bicinchoninic acid (BCA), two colorimetric Cu(I) indicators in common use. The Cu(I) coordination structures were characterized by X-ray absorption spectroscopy. The data presented here facilitate comparison of the isoforms' Cu-binding interactions and contribute to our understanding of the role of Aß peptides as copper chelators in healthy and diseased brains.