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Concentration‐Dependent Interactions of Amphiphilic PiB Derivative Metal Complexes with Amyloid Peptides Aβ and Amylin**
- Source :
- Chemistry – A European Journal, Chemistry-A European Journal, Chemistry-A European Journal, Wiley-VCH Verlag, 2021, 27, pp.2009-2020. ⟨10.1002/chem.202004000⟩, Chemistry-A European Journal, 2021, 27, pp.2009-2020. ⟨10.1002/chem.202004000⟩
- Publication Year :
- 2021
-
Abstract
- International audience; 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 Aβ 1‐40 ( K d = 4.4 nM) and amylin ( K d = 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 Aβ 1‐40 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 Aβ 1‐40 is involved in the interaction between the monomer peptide and the Gd 3+ complex. Finally, ex vivo biodistribution experiments were conducted in healthy mice by using 111 In labelled analogues. Their pancreatic uptake, ~3%ID/g, is promising to envisage amylin imaging in diabetic animals.
- Subjects :
- Biodistribution
Amyloid
[SDV]Life Sciences [q-bio]
Amylin
Peptide
010402 general chemistry
01 natural sciences
Catalysis
Mice
Alzheimer Disease
Coordination Complexes
[CHIM] Chemical Sciences
Amphiphile
Animals
[CHIM]Chemical Sciences
Tissue Distribution
Surface plasmon resonance
Amylin binding
chemistry.chemical_classification
Amyloid beta-Peptides
010405 organic chemistry
Chemistry
Organic Chemistry
General Chemistry
Peptide Fragments
0104 chemical sciences
Islet Amyloid Polypeptide
[SDV] Life Sciences [q-bio]
Biophysics
Linker
Subjects
Details
- ISSN :
- 09476539 and 15213765
- Database :
- OpenAIRE
- Journal :
- Chemistry – A European Journal
- Accession number :
- edsair.doi.dedup.....c90b7022bc033aca54df52d252e02bdf
- Full Text :
- https://doi.org/10.1002/chem.202004000