Raman Spectroscopy with 2D Perturbation Correlation Moving Windows for the Characterization of Heparin–Amyloid Interactions

Townsend, David and Middleton, David and Ashton, Lorna (2020) Raman Spectroscopy with 2D Perturbation Correlation Moving Windows for the Characterization of Heparin–Amyloid Interactions. Analytical Chemistry. ISSN 0003-2700

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Abstract

It has been shown extensively that glycosaminoglycan (GAG)–protein interactions can induce, accelerate, and impede the clearance of amyloid fibrils associated with systemic and localized amyloidosis. Obtaining molecular details of these interactions is fundamental to our understanding of amyloid disease. Consequently, there is a need for analytical approaches that can identify protein conformational transitions and simultaneously characterize heparin interactions. By combining Raman spectroscopy with two-dimensional (2D) perturbation correlation moving window (2DPCMW) analysis, we have successfully identified changes in protein secondary structure during pH- and heparin-induced fibril formation of apolipoprotein A-I (apoA-I) associated with atherosclerosis. Furthermore, from the 2DPCMW, we have identified peak shifts and intensity variations in Raman peaks arising from different heparan sulfate moieties, indicating that protein–heparin interactions vary at different heparin concentrations. Raman spectroscopy thus reveals new mechanistic insights into the role of GAGs during amyloid fibril formation.

Item Type:
Journal Article
Journal or Publication Title:
Analytical Chemistry
Additional Information:
This document is the Accepted Manuscript version of a Published Work that appeared in final form in Analytical Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acs.analchem.0c02390
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1600/1602
Subjects:
ID Code:
147974
Deposited By:
Deposited On:
06 Oct 2020 10:55
Refereed?:
Yes
Published?:
Published
Last Modified:
25 Oct 2020 07:24