1. Investigation of DMSO-Induced Conformational Transitions in Human Serum Albumin Using Two-Dimensional Raman Optical Activity Spectroscopy
- Author
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Vanderlan da Silva Bolzani, Maysa Furlan, Andrea N. L. Batista, Ewan W. Blanch, Lorna Ashton, and João M. Batista
- Subjects
Pharmacology ,Conformational change ,Chemistry ,Dimethyl sulfoxide ,Organic Chemistry ,Human serum albumin ,Catalysis ,Analytical Chemistry ,chemistry.chemical_compound ,Crystallography ,symbols.namesake ,Raman Optical Activity Spectroscopy ,Drug Discovery ,medicine ,symbols ,Raman optical activity ,Raman spectroscopy ,Protein secondary structure ,Spectroscopy ,medicine.drug ,Polyproline helix - Abstract
Recent Raman and Raman optical activity (ROA) results have demonstrated that dimethyl sulfoxide (DMSO) induces the selective conversion of α-helix motifs into the poly(L-proline) II (PPII) helix conformation in an array of proteins, while β-sheets remain mostly unaffected. Human serum albumin (HSA), a highly α-helical protein, underwent the most dramatic changes and, therefore, was selected as a model for further investigations into the mechanism of this conformational change. Herein we report the use of two-dimensional ROA correlation analysis applying synchronous, autocorrelation, and moving windows approaches in order to understand the conformational transitions in HSA as a function of DMSO concentration. Our results indicate that the destabilization of native α-helix starts at DMSO concentrations as little as 20% in water (v/v), with the transition to PPII helix being complete at ~80% DMSO. These results clearly indicate that any protein preparation containing relatively low concentrations of DMSO should consider possible disruptions in α-helical domains.
- Published
- 2014
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