SDS-induced Peptide Conformational Changes: From Triglycyl-glycine to Amyloid-β Oligomers Associated with Alzheimer’s Disease

Abstract

Sodium dodecyl sulfate (SDS) was introduced in polyacrylamide gel electrophoresis (PAGE) due to its capacity of helping proteins to become fully denatured and dissociated from each other. Numerous studies which have been undertaken, using electrospray ionization mass spectrometry (ESI–MS), reported on the process of peptide oligomerization. Many of these investigations have included tetraglycine (H2N–Gly–Gly–Gly–Gly–COOH; G4) as model peptide. The aim of this research is to investigate the effect of SDS on G4 oligomerization, and, especially, to emphasize the dismantling of oligomers under micellar conditions. In water, G4 peptide develops dimers and oligomers, which can also be evidenced in high proportion by MS in the gas phase. Although our results show that SDS is able to reduce the proportion of G4 oligomers, the aqueous G4-SDS system may contain G4 dimers, G4-SDS adducts alongside with the expected monomers and some alkaline metal adducts. The mechanism by which SDS disassembled G4 dimers, which includes sodium ion affinity toward negatively charged carboxyl and sulfonyl groups, was also discussed. Amyloid-β peptide1–40 conformation changed considerably and, especially, the proportion of α-helical populations increased upon SDS binding in a concentration-dependent manner. Molecular dynamics studies confirmed the tendency of Aβ molecules to form α-helical conformers, as the CD and FTIR studies showed.