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Conformational Preferences of Aβ25-35 and Aβ35-25 in Membrane Mimicking Environments

[ Vol. 26 , Issue. 5 ]

Author(s):

Dhandayuthapani Sambasivam, Senthilkumar Sivanesan, Sayeeda Sultana and Jayakumar Rajadas*   Pages 386 - 390 ( 5 )

Abstract:


Background: The structural transition of aggregating Abeta peptides is the key event in the progression of Alzheimer’s Disease (AD).

Objective: In the present work, the structural modifications of toxic Aβ25-35 and the scrambled Aβ35-25 were studied in Trifluoroethanol (TFE) and in aqueous SDS micelles.

Methods: Using CD spectroscopic investigations, the conformational transition of Aβ25-35 and Aβ35-25 peptides were determined in different membrane mimicking environments such as TFE and SDS. An interval scan CD of the peptides on evaporation of TFE was performed. TFE titrations were carried out to investigate the intrinsic ability of the structural conformations of peptides.

Results: We show by spectroscopic evidence that Aβ25-35 prefers beta sheet structures upon increasing TFE concentrations. On the other hand, the non-toxic scrambled Aβ35-25 peptide only undergoes a transition from random coil to α-helix conformation with increasing TFE. In the interval scan studies, Aβ25-35 did not show any structural transitions, whereas Aβ35-25 showed transition from α-helix to β-sheet conformation. In membrane simulating aqueous SDS micelles, Aβ25-35 showed a transition from random coil to α-helix while Aβ35-25 underwent transition from random coil to β-sheet conformation.

Conclusion: Overall, the current results seek new insights into the structural properties of amyloidogenic and the truncated sequence in membrane mimicking solvents.

Keywords:

Alzheimer's disease, aggregation, conformation, amyloid fragments, membrane environment, membrane mimicking solvents.

Affiliation:

Bioorganic Chemistry Laboratory, Central Leather Research Institute, Adyar, Chennai 600 020, Bioorganic Chemistry Laboratory, Central Leather Research Institute, Adyar, Chennai 600 020, Department of Chemistry, St Peter's Institute of Higher Education and Research, Chennai-600054, Bioorganic Chemistry Laboratory, Central Leather Research Institute, Adyar, Chennai 600 020

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