Self-assembled monolayers of Aβ peptides on Au electrodes: an artificial platform for probing the reactivity of redox active metals and cofactors relevant to Alzheimer's disease.
The water-soluble hydrophilic part of human Aβ peptide has been extended to include a C-terminal cysteine residue. Utilizing the thiol functionality of this cysteine residue, self-assembled monolayers (SAM) of these peptides are formed on Au electrodes. Atomic force microscopy imaging confirms formation of small Aβ aggregates on the surface of the electrode. These aggregates bind redox active metals like Cu and cofactors like heme, both of which are proposed to generate toxic partially reduced oxygen species (PROS) and play a vital role in Alzheimer's disease. The spectroscopic and electrochemical properties of these Cu and heme bound Aβ SAM are similar to those reported for the soluble Cu and heme bound Aβ peptide. Experiments performed on these Aβ-SAM electrodes clearly demonstrate that (1) heme bound Aβ is kinetically more competent in reducing O(2) than Cu bound Aβ, (2) under physiological conditions the reduced Cu site produces twice as much PROS (measured in situ) than the reduced heme site, and (3) chelators like clioquinol remove Cu from these aggregates, while drugs like methylene blue inhibit O(2) reactivity of the heme cofactor. This artificial construct provides a very easy platform for investigating potential drugs affecting aggregation of human Aβ peptides and PROS generation by its complexes with redox active metals and cofactors.
Department of Inorganic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, India, 700032.
Debajyoti
D
Pramanik
Kushal
K
Sengupta
Soumya
S
Mukherjee
Somdatta Ghosh
SG
Dey
Abhishek
A
Dey
D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000378:metabolism*; D004566:Electrodes; D006046:Gold / Q000737:chemistry; D006418:Heme / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D013499:Surface Properties
D016229:Amyloid beta-Peptides; D002614:Chelating Agents; D006418:Heme; D006046:Gold; D003300:Copper; D006861:Hydrogen Peroxide; D010100:Oxygen