study of cis–trans isomerization mechanism of [3-(3-aminomethyl) phenylazo] phenyl acetic acid as a causative role in alzheimer using density functional theory

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