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Metal chelates targeted to amyloid peptides are widely explored as diagnostic tools or therapeutic agents. The attachment of a metal complex to amyloid recognition units typically leads to a decrease in peptide affinity. We show here that by separating a macrocyclic GdL chelate and a PiB targeting unit with a long hydrophobic C10 linker, it is possible to attain nanomolar affinities for both Aβ1‐40 (Kd=4.4 nm) and amylin (Kd=4.5 nm), implicated, respectively in Alzheimer's disease and diabetes. The Scatchard analysis of surface plasmon resonance data obtained for a series of amphiphilic, PiB derivative GdL complexes indicate that their Aβ1‐40 or amylin binding affinity varies with their concentration, thus micellar aggregation state. The GdL chelates also affect peptide aggregation kinetics, as probed by thioflavin‐T fluorescence assays. A 2D NMR study allowed identifying that the hydrophilic region of Aβ1‐40 is involved in the interaction between the monomer peptide and the Gd3+ complex. Finally, ex vivo biodistribution experiments were conducted in healthy mice by using 111In labeled analogues. Their pancreatic uptake, ∼3 %ID g−1, is promising to envisage amylin imaging in diabetic animals. [ABSTRACT FROM AUTHOR]

Front Cover: Concentration-Dependent Interactions of Amphiphilic PiB Derivative Metal Complexes with Amyloid Peptides A and Amylin (Chem. Eur. J. 6/2021) Keywords: amylin; amyloid peptide; A ; metal complex; micellar aggregation EN amylin amyloid peptide A metal complex micellar aggregation 1860 1860 1 01/29/21 20210126 NES 210126 B Metal chelates targeted to amyloid peptides b are widely explored as diagnostic tools or therapeutic agents. Amylin, amyloid peptide, A , metal complex, micellar aggregation. [Extracted from the article]