Hamid Reza Guodarzi; Mohammad Agha Mohammadi; Mohsen Mousavi1
Volume 1, Issue 11 , November 2013, , Pages 1512-1517
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 ...
Read More
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 acetic acid (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
![Study of Cis–trans Isomerization Mechanism of [3-(3-Aminomethyl) Phenylazo] Phenyl Acetic Acid as a Causative Role in Alzheimer Using Density Functional Theory](data/ijabbr/coversheet/cover_en.jpg)