Biphenyl ethers conjugated CdSe/ZnS core/shell quantum dots and interpretation of the mechanism of amyloid fibril disruption.
The biphenyl ethers (BPEs) are the potent inhibitors of TTR fibril formation and are efficient fibril disrupter. However, the mechanism by which the fibril disruption occurs is yet to be fully elucidated. To gain insight into the mechanism, we synthesized and used a new QD labeled BPE to track the process of fibril disruption. Our studies showed that the new BPE-QDs bind to the fiber uniformly and has affinity and specificity for TTR fiber and disrupted the pre-formed fiber at a relatively slow rate. Based on these studies we put forth the probable mechanism of fiber disruption by BPEs. Also, we show here that the BPE-QDs interact with high affinity to the amyloids of Abeta(42), lysozyme and insulin. The potential of BPE-QDs in the detection of senile plaque in the brain of transgenic Alzheimer's mice has also been explored.
Gupta
Sarika
S
National Institute of Immunology, Aruna Asaf Ali marg, New Delhi 110067, India. sarika@nii.res.in
Babu
Ponnusamy
P
Surolia
Avadhesha
A
D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019187:Cadmium Compounds / Q000737:chemistry*; D004987:Ethers / Q000494:pharmacology*; D005456:Fluorescent Dyes / Q000378:metabolism; D007368:Interferometry; D051379:Mice; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D011228:Prealbumin / Q000737:chemistry / Q000378:metabolism; D020836:Protein Structure, Quaternary; D045663:Quantum Dots; D018036:Selenium Compounds / Q000737:chemistry*; D013379:Substrate Specificity / Q000187:drug effects; D013440:Sulfides / Q000737:chemistry*; D014260:Triclosan / Q000737:chemistry; D017967:Zinc Compounds / Q000737:chemistry*
D000682:Amyloid; D001713:Biphenyl Compounds; D019187:Cadmium Compounds; D004987:Ethers; D005456:Fluorescent Dyes; D011228:Prealbumin; D018036:Selenium Compounds; D013440:Sulfides; D014260:Triclosan; D017967:Zinc Compounds; C010574:biphenyl; C058667:cadmium selenide; C031238:zinc sulfide