Association constants of pyridine and piperidine alkaloids to amyloid beta peptide determined by electrochemical impedance spectroscopy.
Amyloid beta(1-40) peptide was immobilized on an Au-colloid modified gold electrode and an electrochemical impedance spectroscopy (EIS) system was elaborated for determining the association constants, K(a), between small molecular ligands and the peptide. The changes in the resistance of the modified electrode layer with deposited Abeta(1-40) peptide were measured with EIS in relation to a series of concentrations of the ligands studied. The association constants were calculated from Langmuir isotherms. The method is sensitive, reproducible and consumes only very little amounts of interacting species. The method was applied to determine the affinity of a series of pyridine and piperidine derivatives, mainly alkaloids of a known ability, to cross the blood-brain barrier. Along with nicotine and its main metabolite cotinine, the following agents were taken for the study: anabasine, arecoline, coniine, lobeline, pseudopelletierine, trigonelline, as well as pyridine and piperidine themselves. For the sake of comparison, two vitamins were also subjected to the study: ascorbic acid and pyridoxine. There was no association of these vitamins, which were tested as a negative control. For the compounds studied, a strong association with Abeta(1-40) was determined with K(a) ranging from 1.7 x 10(7) M(-1) for (+/-)-anabasine to 2.3 x 10(8) M(-1) for arecoline hydrobromide. As a positive control, a well known amyloid specific binder, Congo Red, was tested, displaying K(a) equal to 3.7 x 10(8) M(-1).
Grabowska
Iwona
I
Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
Radecka
Hanna
H
Burza
Anna
A
Radecki
Jerzy
J
Kaliszan
Michał
M
Kaliszan
Roman
R
D000470:Alkaloids / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000737:chemistry*; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D017097:Electric Impedance; D004563:Electrochemistry; D004566:Electrodes; D006801:Humans; D008853:Microscopy; D009538:Nicotine / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D011725:Pyridines / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics
D000470:Alkaloids; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010880:Piperidines; D011725:Pyridines; C078592:amyloid beta-protein (1-40); D009538:Nicotine