Surface-enhanced Raman spectroscopy for drug discovery: peptide-RNA binding.
Surface-enhanced Raman spectroscopy for drug discovery: peptide-RNA binding.
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DOI：
10.1007/s00216-022-04190-5
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发表时间：
2022-08
影响因子：
4.3
通讯作者：
Lednev, Igor K.
中科院分区：
文献类型：
--
作者：
Almehmadi, Lamyaa M.;Valsangkar, Vibhav A.;Halvorsen, Ken;Zhang, Qiang;Sheng, Jia;Lednev, Igor K.
对新药不断增长的需求突出了开发新的成本和时间有效的药物发现技术的必要性。表面增强拉曼光谱（Sers）是一种新兴的超灵敏和无标记技术，可以有效地检测和表征分子间的相互作用。我们最近开发了一种Sers平台，用于检测与金基底连接的单个蛋白质分子（Almehmadi et al. Scientific Reports 2019）。在这项研究中，我们扩展了这种方法来探测潜在药物与RNA靶点的结合。为了证明概念的证据，测试了两种具有接近的一级结构和对与强直性肌营养不良相关的RNA CUG重复的不同结合亲和力的16个氨基酸残基的肽。使用开发的方法探测了三微升的RNA重复序列与这些肽在纳摩尔浓度的溶液，并证明了只有一种肽的结合。SER光谱表现出明显的波动沿着突然强烈增强，因为光谱是从单个点连续收集的。SER光谱数据集的主成分分析（PCA）表明，游离的RNA重复序列可以100%的准确度从那些与肽复合区分。Sers平台的发展为药物发现提供了一个新的机会，RNA结合肽的无标记筛选。本研究开发的用于药物发现的Sers平台的示意图
The ever-growing demand for new drugs highlights the need to develop novel cost- and time-effective techniques for drug discovery. Surface-enhanced Raman spectroscopy (SERS) is an emerging ultrasensitive and label-free technique that allows for the efficient detection and characterization of molecular interactions. We have recently developed a SERS platform for detecting a single protein molecule linked to a gold substrate (Almehmadi et al. Scientific Reports 2019). In this study, we extended the approach to probe the binding of potential drugs to RNA targets. To demonstrate the proof of concept, two 16-amino acid residue peptides with close primary structures and different binding affinities to the RNA CUG repeat related to myotonic dystrophy were tested. Three-microliter solutions of the RNA repeat with these peptides at nanomolar concentrations were probed using the developed approach, and the binding of only one peptide was demonstrated. The SER spectra exhibited significant fluctuations along with a sudden strong enhancement as spectra were collected consecutively from individual spots. Principal component analysis (PCA) of the SER spectral datasets indicated that free RNA repeats could be differentiated from those complexed with a peptide with 100% accuracy. The developed SERS platform provides a novel opportunity for label-free screening of RNA-binding peptides for drug discovery. Schematic representation of the SERS platform for drug discovery developed in this study
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影响因子：
64.5
作者：
Cooper TA;Wan L;Dreyfuss G
通讯作者：
Dreyfuss G
DOI：
10.1016/j.saa.2010.08.034
发表时间：
2010-12-01
影响因子：
4.4
作者：
Culka, A.;Jehlicka, J.;Edwards, H. G. M.
通讯作者：
Edwards, H. G. M.
影响因子：
38.3
作者：
Lindquist, Nathan C.;de Albuquerque, Carlos Diego L.;Brolo, Alexandre G.
通讯作者：
Brolo, Alexandre G.
影响因子：
--
作者：
Konigsberg, W
通讯作者：
Konigsberg, W
影响因子：
29.4
作者：
Chirumamilla, Manohar;Toma, Andrea;Di Fabrizio, Enzo
通讯作者：
Di Fabrizio, Enzo