Differential sensing with arrays of de novo designed peptide assemblies.

Differential sensing with arrays of de novo designed peptide assemblies.
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具有从头设计的肽组件阵列的差异传感。

DOI:
10.1038/s41467-023-36024-y
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发表时间:
2023-01-24
影响因子:
16.6
通讯作者:
Woolfson, Derek N.
Woolfson, Derek N.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Dawson, William M.;Shelley, Kathryn L.;Fletcher, Jordan M.;Scott, D. Arne;Lombardi, Lucia;Rhys, Guto G.;LaGambina, Tania J.;Obst, Ulrike;Burton, Antony J.;Cross, Jessica A.;Davies, George;Martin, Freddie J. O.;Wiseman, Francis J.;Brady, R. Leo;Tew, David;Wood, Christopher W.;Woolfson, Derek N.

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差分传感试图模仿哺乳动物的嗅觉和味觉来识别分析物和复杂的混合物。差分传感器取代了数百个复杂的、膜结合的G蛋白偶联受体,采用了小分子阵列。在这里,我们表明,计算设计的从头肽阵列提供了替代的合成受体的差异传感。我们使用自组装α-螺旋桶(α HB),其中心通道可以可预测地改变以改变其大小,形状和化学性质。通道容纳在结合时发荧光的环境敏感染料。用分析物填充装载染料的桶的阵列引起差分荧光团位移。所得到的荧光指纹被用于训练将模式与分析物相关联的机器学习模型。我们表明,该系统区分一系列的生物分子,饮料和诊断相关的生物样品。由于α HB具有耐用性和化学多样性,因此该系统具有在各种环境中检测许多分析物的潜力。差分传感的目的是通过使用合成受体来模拟味觉和嗅觉等感官。在这里,作者表明,从头设计的肽组件阵列可以用作传感器组件,以区分各种分析物和复杂的混合物。
Differential sensing attempts to mimic the mammalian senses of smell and taste to identify analytes and complex mixtures. In place of hundreds of complex, membrane-bound G-protein coupled receptors, differential sensors employ arrays of small molecules. Here we show that arrays of computationally designed de novo peptides provide alternative synthetic receptors for differential sensing. We use self-assembling α-helical barrels (αHBs) with central channels that can be altered predictably to vary their sizes, shapes and chemistries. The channels accommodate environment-sensitive dyes that fluoresce upon binding. Challenging arrays of dye-loaded barrels with analytes causes differential fluorophore displacement. The resulting fluorimetric fingerprints are used to train machine-learning models that relate the patterns to the analytes. We show that this system discriminates between a range of biomolecules, drink, and diagnostically relevant biological samples. As αHBs are robust and chemically diverse, the system has potential to sense many analytes in various settings. Differential sensing aims to mimic senses such as taste and smell through the use of synthetic receptors. Here, the authors show that arrays of de novo designed peptide assemblies can be used as sensor components to distinguish various analytes and complex mixtures.
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