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2017 ; 2
(7
): 3192-3200
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gab.com Text
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English Wikipedia
Substituent, Charge, and Size Effects on the Fluorogenic Performance of Amyloid
Ligands: A Small-Library Screening Study
#MMPMID30023689
Donabedian PL
; Evanoff M
; Monge FA
; Whitten DG
; Chi EY
ACS Omega
2017[Jul]; 2
(7
): 3192-3200
PMID30023689
show ga
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 the fluorescence
yield. These principles can serve as a guide for the further refinement of the
effective amyloid-sensing molecules.