Tuning the Solution Self-Assembly of a Peptide-PEG (Polyethylene Glycol) Conjugate with a-Cyclodextrin.
Tuning the Solution Self-Assembly of a Peptide-PEG (Polyethylene Glycol) Conjugate with a-Cyclodextrin.
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调整肽-PEG（聚乙二醇）缀合物与α-环糊精的溶液自组装。
DOI：
10.1002/cbic.202300472
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Castelletto V
中科院分区：
文献类型：
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作者：
Castelletto V
环糊精是糖环分子，其充当主体空腔，可以包封小的客体分子或使聚合物链形成线状。我们研究了α-环糊精（αCD）对我们小组先前研究的肽-聚合物缀合物YYKLVFF-PEG 3 K的水溶液自组装的影响[Castellettoet al.， Polym.化学成分：2010，1，453-459]。该缀合物包含设计的淀粉样蛋白形成肽YYKLVFF，其含有来自淀粉样蛋白β肽Aβ16 - 20的KLVFF序列，沿着两个芳香族酪氨酸残基以增强疏水性，以及摩尔质量为3 kg mol−1的聚乙二醇PEG。 缀合物在水溶液中自组装成β折叠原纤维。在这里，我们表明与αCD的络合在水溶液中产生自由浮动的纳米片（具有β片结构）。纳米片包含具有疏水肽核心和高度溶胀的PEG外层的双层。从原纤维到纳米片的转变是由PEG链上的αCD分子数量增加驱动的，正如1H NMR光谱所确定的。这些发现指出使用环糊精添加剂作为调节肽-聚合物缀合物和潜在的其他聚合物/生物分子杂化物中的溶液自组装的有力手段。
Cyclodextrins are saccharide ring molecules which act as host cavities that can encapsulate small guest molecules or thread polymer chains. We investigate the influence of alpha‐cyclodextrin (αCD) on the aqueous solution self‐assembly of a peptide‐polymer conjugate YYKLVFF‐PEG3K previously studied by our group [Castellettoet al.,Polym. Chem., 2010, 1, 453–459]. This conjugate comprises a designed amyloid‐forming peptide YYKLVFF that contains the KLVFF sequence from Amyloid β peptide, Aβ16‐20, along with two aromatic tyrosine residues to enhance hydrophobicity, as well as polyethylene glycol PEG with molar mass 3 kg mol−1. The conjugate self‐assembles into β‐sheet fibrils in aqueous solution. Here we show that complexation with αCD instead generates free‐floating nanosheets in aqueous solution (with a β‐sheet structure). The nanosheets comprise a bilayer with a hydrophobic peptide core and highly swollen PEG outer layers. The transition from fibrils to nanosheets is driven by an increase in the number of αCD molecules threaded on the PEG chains, as determined by1H NMR spectroscopy. These findings point to the use of cyclodextrin additives as a powerful means to tune the solution self‐assembly in peptide‐polymer conjugates and potentially other polymer/biomolecular hybrids.