Shanghai Food Safety and Engineering Technology Research Center, Key Lab of Urban Agriculture (South), Bor S. Luh Food Safety Research Center, School of Agriculture & Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
Shanghai Food Safety and Engineering Technology Research Center, Key Lab of Urban Agriculture (South), Bor S. Luh Food Safety Research Center, School of Agriculture & Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
Int J Biol Macromol. 2020 Dec 1;164:3932-3942. doi: 10.1016/j.ijbiomac.2020.09.005. Epub 2020 Sep 6.
Chronic hyperglycemia results in the formation of advanced glycation end-products (AGEs) and triggers amyloid fibril formation. Molecules designed to inhibit amyloid fibrils function by eliminating toxic oligomers or reducing fibril formation. Here, the bioactivity of polyphenols in redirecting the self-assembly of amyloid fibrils was reported through microscopic, spectroscopic and molecular docking studies. Our findings illustrate that glycation causes BSA to self-assemble into amyloid fibrils. 17 Lys residues had modified to carboxy methyl lysine (CML) but only Lys523 was probable of modifying into carboxy ethyl lysine (CEL). In contrast, only 6 Arg residues are identified to be modified to Argpyrimidine (Arg-p). A simple polyphenol baicalein (BLN) redirect the self-assembly of amyloid fibrils into off-pathway hybrid nanostructures. Circular dichroism spectroscopic studies suggested that in the presence of BLN helical conformation was favored. Molecular modeling studies suggested that hydrogen bonding and hydrophobic interaction of polyphenols preferentially at crucial amyloidogenic regions can hinder amyloid fibrillation (Phe133, Lys136, Tyr137, Ile141, Tyr160 and Arg185). Mass spectrometric results illustrated that the presence of a simple polyphenol BLN several residues are unmodified to CML, CEL or Arg-p. Together, our findings suggest that polyphenols could have a protective effect and the redirection can help alleviate the amyloid fibril formation.
慢性高血糖导致晚期糖基化终产物（AGEs）的形成，并触发淀粉样纤维的形成。旨在抑制淀粉样纤维形成的分子通过消除毒性寡聚体或减少纤维形成来发挥作用。在这里，通过微观、光谱和分子对接研究报告了多酚重新引导淀粉样纤维自组装的生物活性。我们的研究结果表明，糖化导致 BSA 自组装成淀粉样纤维。17 个赖氨酸残基被修饰为羧甲基赖氨酸（CML），但只有赖氨酸 523 可能被修饰为羧乙基赖氨酸（CEL）。相比之下，只有 6 个精氨酸残基被鉴定为精氨酸嘧啶（Arg-p）。一种简单的多酚白杨素（BLN）将淀粉样纤维的自组装重新引导到非途径杂化纳米结构中。圆二色光谱研究表明，在 BLN 的存在下，螺旋构象占优势。分子建模研究表明，多酚的氢键和疏水相互作用优先在关键的淀粉样形成区域，可以阻止淀粉样纤维形成（phe133、lys136、tyr137、ile141、tyr160 和 arg185）。质谱结果表明，存在简单多酚 BLN 时，几个残基未被修饰为 CML、CEL 或 Arg-p。总之，我们的研究结果表明，多酚可能具有保护作用，重定向可以帮助减轻淀粉样纤维的形成。
