ABSTRACT
We present structural models for three different amyloid fibril polymorphs prepared from amylin20-29 (sequence SNNFGAILSS) and amyloid-ß25-35 (Aß25-35) (sequence GSNKGAIIGLM) peptides. These models are based on the amide C=O bond and Ramachandran ψ-dihedral angle data from Raman spectroscopy, which were used as structural constraints to guide molecular dynamics (MD) simulations. The resulting structural models indicate that the basic structural motif of amylin20-29 and Aß25-35 fibrils is extended ß-strands. Our data indicate that amylin20-29 forms both antiparallel and parallel ß-sheet fibril polymorphs, while Aß25-35 forms a parallel ß-sheet fibril structure. Overall, our work lays the foundation for using Raman spectroscopy in conjunction with MD simulations to determine detailed molecular-level structural models of amyloid fibrils in a manner that complements gold-standard techniques, such as solid-state nuclear magnetic resonance and cryogenic electron microscopy.
Subject(s)
Amyloid , Spectrum Analysis, Raman , Amyloid/chemistry , Amyloid beta-Peptides/chemistry , Peptide Fragments/chemistry , Magnetic Resonance Spectroscopy/methods , Molecular Dynamics Simulation , AmidesABSTRACT
A facile platform derived from deposition of ethynyl linkers on carbon fiber microelectrodes has been developed for sensitive and selective sensing of Cu(ii). This study is the first to demonstrate the successful anodic deposition of ethynyl linkers, specifically 1,4-diethynylbenzene, onto carbon fiber microelectrodes. Multi-scan deposition of DEB on these microelectrodes resulted in an increased sensitivity and selectivity towards Cu(ii) that persists amidst other divalent interferents and displays sustained performance over four days while stored at room temperature. This method can be extended to other ethynyl terminal moieties, thereby creating a versatile chemical platform that will enable improved sensitivity and selectivity for a new frontier of biomarker measurement.
