Substituent, Charge, and Size Effects on the Fluorogenic Performance of Amyloid Ligands: A Small-Library Screening Study

ACS Omega
Patrick L DonabedianEva Y Chi

Abstract

Developing new molecular ligands for the direct detection and tracking of amyloid protein aggregates is key to understanding and defeating myriad neurodegenerative and other disorders including Alzheimer's and Parkinson's diseases. A crucial factor in the performance of an amyloid dye is its ability to detect the amyloid structural motif independent of the sequence of the amyloid-forming protomer. The current study investigates structure-function relationships of a class of novel phenyleneethynylene (PPE)-based dyes and fluorescent polymers using amyloid fibrils formed by two model proteins: lysozyme and insulin. A small library of 18 PPE compounds that vary in molecular weights, charge densities, water solubilities, and types and geometries of functional groups was tested. One compound, the small anionic oligo(p-phenylene ethynylene) electrolyte OPE1, was identified as a selective sensor for the amyloid conformation of both lysozyme and insulin. On the basis of protein binding and photophysical changes observed in the dye from this set of PPE compounds, keys to the selective detection of the amyloid protein conformation include moderate size, negative charge, and substituents that provide high microenvironment sensitivity to t...Continue Reading

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Citations

Jan 31, 2019·Advanced Materials·Bing WangGuillermo C Bazan
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chiara Maria Antonietta GangemiPaola Maria Bonaccorsi
Dec 4, 2020·ACS Applied Materials & Interfaces·Florencia A MongeAlison M Kell
Jul 31, 2018·Langmuir : the ACS Journal of Surfaces and Colloids·David G WhittenEva Y Chi

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Methods Mentioned

BETA
circular dichroism
Fluorescence
AFM

Software Mentioned

AVIV
OriginPro

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