Study of Cis–trans Isomerization Mechanism of [3-(3-Aminomethyl) Phenylazo] Phenyl acetic Acid as a Causative Role in Alzheimer Using Density Functional Theory

Publish Year: 1392
نوع سند: مقاله ژورنالی
زبان: English
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شناسه ملی سند علمی:

JR_IJABBR-1-11_014

تاریخ نمایه سازی: 26 اسفند 1394

Abstract:

Amyloid-β (Aβ) self-assembly into cross-β amyloidfibrils is implicated in a causative role in Alzheimer’s disease pathology.Uncertainties persist regarding the mechanisms of amyloid self assembly and the role of metastable prefibrillar aggregates. Aβ fibrilsfeature a sheet-turn-sheet motif in the constituent β- strands; as such, turn nucleation has been proposed as a rate-limiting step in the self assembly pathway. Herein, we report the use of an azobenzene β-hairpin mimetic to study byUsing Density Functional Theory the role turn nucleation plays on Aβ self assembly.[3-(3-Aminomethyl) phenylazo] phenyl aceticacid (AMPP)was incorporated into the putative turn region of Aβ42 to elicit temporal control over Aβ42 turn nucleation; it was hypothesized that self-assembly would be favored in the cis-AMPP conformation if β-hairpin formation occurs during Aβ self-assembly and that the trans-AMPP conformer would display attenuated fibrillization propensity. It was unexpectedly observed that the trans-AMPP Aβ42Additionally, cis-trans photo isomerization resulted in rapid formation of native-like amyloid fibrils and trans−cis conversion in the fibril state reduced the population of native-like fibrils. Thus, temporal photo control over Aβ turn conformation providessignificant insight into Aβ self-assembly

Authors

Hamid Reza Guodarzi

Department of Chemistry, Saveh Branch, Islamic azad University, Saveh, Iran

Mohammad. Agha Mohammadi

Department of Chemistry, Bourojerd Branch, Islamic Azad University, Bourojerd, Iran

Mohsen Mousavi

Department of Chemistry, Saveh Branch, Islamic azad University, Saveh, Iran