An experimental evidence for the key role of diphenylalanine in fibril formation

摘要

This study examined the role of diphenylalanine(the central hydrophobic cluster of Alzheimer's β-amyloid peptide)in the intermolecular hydrogen-bonded supramolecular sheet and fibril formation.N-phenylglycine appended peptide NPG-Phe-Phe-OMe(1),having a sequence similarity with a diphenylalanine motif,self-aggregates to form entangled fibers.The fibers show green-gold birefringence in a Congo red assay.Moreover,the fibers bind with thioflavin T(ThT)and show an enhanced emission.However,the tyrosine-modified analogues failed to form fibers and rather exhibited a microsphere-like morphology.From X-ray diffraction analysis,the tyrosine-modified analogues,namely,NPG-Phe-Tyr-OMe(2)and NPG-Tyr-Phe-OMe(3),adopt extended conformations and self-aggregate to form sheet-like structures via intermolecular hydrogen bonds and π-π stacking interactions.