Altering Peptide Fibrillization by Polymer Conjugation
Altering Peptide Fibrillization by Polymer Conjugation
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DOI：
10.1021/bm3007117
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发表时间：
2012-09-01
影响因子：
6.2
通讯作者：
Perrier, Sebastien
中科院分区：
文献类型：
--
作者：
Dehn, Sabrina;Castelletto, Valeria;Perrier, Sebastien
提出了一种策略，其利用不同性质的合成聚合物的能力来干扰基于淀粉样蛋白的β折叠形成肽的强自组装能力。遵循收敛方法，通过固相肽合成（SPPS）合成感兴趣的肽，并通过可逆加成-断裂链转移（RAFT）聚合合成聚合物，然后通过铜（I）催化的叠氮化物-炔环加成（CuAAC）生成所需的肽-聚合物缀合物。这项研究的重点是β-淀粉样肽（A β），A β（16-20）（KLVFF）的核心序列的修改版本。通过红外光谱、透射电镜、圆二色谱和小角X射线散射研究了短链聚（N-异丙基丙烯酰胺）和聚（丙烯酸羟乙酯）对杂化材料自组装性能的影响。研究结果表明，连接这些聚合物在一定程度上扰乱了生物分子的强自组装特性，并允许根据肽的β折叠形成能力影响肽的聚集。这项研究提出了一种创新的途径，旨在有针对性地和受控地组装淀粉样纤维，以驱动聚合物纳米材料的形成。
A strategy is presented that exploits the ability of synthetic polymers of different nature to disturb the strong self-assembly capabilities of amyloid based beta-sheet forming peptides. Following a convergent approach, the peptides of interest were synthesized via solid-phase peptide synthesis (SPPS) and the polymers via reversible addition-fragmentation chain transfer (RAFT') polymerization, followed by a copper(I) catalyzed azide-alkyne cycloaddition (CuAAC) to generate the desired peptide-polymer conjugates. This study focuses on a modified version of the core sequence of the beta-amyloid peptide (A beta), A beta(16-20) (KLVFF). The influence of attaching short poly(N-isopropylacrylamide) and poly(hydroxyethylacrylate) to the peptide sequences on the self-assembly properties of the hybrid materials were studied via infrared spectroscopy, TEM, circular dichroism and SAXS. The findings indicate that attaching these polymers disturbs the strong self-assembly properties of the biomolecules to a certain degree and permits to influence the aggregation of the peptides based on their beta-sheets forming abilities. This study presents an innovative route toward targeted and controlled assembly of amyloid-like fibers to drive the formation of polymeric nanomaterials.