School of Chemistry, Food Science and Pharmacy, University of Reading, Whiteknights, Reading RG6 6AD, United Kingdom.
Langmuir. 2011 Mar 15;27(6):2980-8. doi: 10.1021/la104495g. Epub 2011 Feb 21.
The dipeptide L-carnosine has a number of important biological properties. Here, we explore the effect of attachment of a bulky hydrophobic aromatic unit, Fmoc [N-(fluorenyl-9-methoxycarbonyl)] on the self-assembly of Fmoc-L-carnosine, i.e., Fmoc-β-alanine-histidine (Fmoc-βAH). It is shown that Fmoc-βAH forms well-defined amyloid fibrils containing β sheets above a critical aggregation concentration, which is determined from pyrene and ThT fluorescence experiments. Twisted fibrils were imaged by cryogenic transmission electron microscopy. The zinc-binding properties of Fmoc-βAH were investigated by FTIR and Raman spectroscopy since the formation of metal ion complexes with the histidine residue in carnosine is well-known, and important to its biological roles. Observed changes in the spectra may reflect differences in the packing of the Fmoc-dipeptides due to electrostatic interactions. Cryo-TEM shows that this leads to changes in the fibril morphology. Hydrogelation is also induced by addition of an appropriate concentration of zinc ions. Our work shows that the Fmoc motif can be employed to drive the self-assembly of carnosine into amyloid fibrils.
二肽 L-肌肽具有许多重要的生物学特性。在这里，我们研究了连接庞大的疏水性芳基单元 Fmoc [N-（芴基-9-甲氧羰基）] 对 Fmoc-L-肌肽，即 Fmoc-β-丙氨酸-组氨酸（Fmoc-βAH）自组装的影响。结果表明，Fmoc-βAH 在临界聚集浓度以上形成具有β片层的明确定义的淀粉样纤维，这是通过芘和 ThT 荧光实验确定的。低温透射电子显微镜成像显示出扭曲的纤维。通过傅里叶变换红外和拉曼光谱研究了 Fmoc-βAH 的锌结合特性，因为众所周知肌肽中的组氨酸残基与金属离子形成配合物，这对其生物学作用很重要。观察到的光谱变化可能反映了由于静电相互作用，Fmoc-二肽的堆积方式存在差异。低温透射电子显微镜显示，这导致了纤维形态的变化。添加适量浓度的锌离子也会诱导水凝胶的形成。我们的工作表明，Fmoc 基序可用于驱动肌肽自组装成淀粉样纤维。
