A reactive peptidic linker for self-assembling hybrid quantum dot-DNA bioconjugates
A reactive peptidic linker for self-assembling hybrid quantum dot-DNA bioconjugates
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DOI：
10.1021/nl070782v
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发表时间：
2007-06-01
期刊：
影响因子：
10.8
通讯作者：
Mattoussi, Hedi
中科院分区：
文献类型：
--
作者：
Medintz, Igor L.;Berti, Lorenzo;Mattoussi, Hedi
蛋白质、肽、DNA 和其他生物分子自组装到半导体量子点 (QD) 是一种有吸引力的生物共轭途径，可以避免与共价化学和后续纯化相关的许多问题。多组氨酸序列已被证明可以通过与纳米晶体表面上未占据的配位金属位点络合，促进蛋白质和肽自组装到 ZnS 涂层的 CdSe QD 上。我们描述了硫醇反应性六组氨酸肽接头的合成和表征，该接头可以化学连接到硫醇化 DNA 寡聚物上，并介导其自组装成 CdSe-ZnS 核壳量子点。利用凝胶电泳和荧光共振能量转移技术探测了六组氨酸 DNA 与 QD 的自组装，结果证实了通过控制每个 QD 组装的 DNA 的平均摩尔比形成高亲和力缀合物。为了证明这种反应性肽接头策略的潜力，我们对原型 QD-DNA 染料分子信标进行了自组装，并针对特定和非特定目标 DNA 进行了测试。这种缀合途径具有潜在的多功能性，因为改变肽接头的反应性可能允许靶向不同的官能团（例如胺）并促进其他纳米颗粒-生物分子结构的自组装。
Self-assembly of proteins, peptides, DNA, and other biomolecules to semiconductor quantum dots (QD) is an attractive bioconjugation route that can circumvent many of the problems associated with covalent chemistry and subsequent purification. Polyhistidine sequences have been shown to facilitate self-assembly of proteins and peptides to ZnS-overcoated CdSe QDs via complexation to unoccupied coordination metal sites on the nanocrystal surface. We describe the synthesis and characterization of a thiol-reactive hexahistidine peptidic linker that can be chemically attached to thiolated-DNA oligomers and mediate their self-assembly to CdSe-ZnS core-shell QDs. The self-assembly of hexahistidine-appended DNA to QDs is probed with gel electrophoresis and fluorescence resonance energy transfer techniques, and the results confirm high-affinity conjugate formation with control over the average molar ratio of DNA assembled per QD. To demonstrate the potential of this reactive peptide linker strategy, a prototype QD-DNA-dye molecular beacon is self-assembled and tested against both specific and nonspecific target DNAs. This conjugation route is potentially versatile, as altering the reactivity of the peptide linker may allow targeting of different functional groups such as amines and facilitate self-assembly of other nanoparticle-biomolecule structures.