使用种群转移模型进行别构抑制剂和激动剂的合理设计：体外验证和在人工生物传感器中的应用。
Rational design of allosteric inhibitors and activators using the population-shift model: in vitro validation and application to an artificial biosensor.
机构信息
Dipartimento di Scienze e Tecnologie Chimiche, University of Rome, Tor Vergata, Via della Ricerca Scientifica, 00133 Rome, Italy.
出版信息
J Am Chem Soc. 2012 Sep 19;134(37):15177-80. doi: 10.1021/ja304672h. Epub 2012 Sep 5.
Abstract
The population-shift mechanism can be used for rational re-engineering of structure-switching biosensors to enable their allosteric inhibition and activation. As a proof-of-principle example of this, we have introduced distal allosteric sites into molecular beacons, which are optical sensors for the detection of specific nucleic acid sequences. The binding of inhibitors and activators to these sites enabled the rational modulation of the sensor's target affinity-and thus its useful dynamic range-over 3 orders of magnitude. The convenience with which this was done suggests that the population-shift mechanism may prove to be a useful method by which allosteric regulation can be introduced into biosensors, "smart" biomaterials, and other artificial biotechnologies.
摘要
人群转移机制可用于理性地重新设计结构转换生物传感器，使其具有变构抑制和激活作用。作为这方面的原理验证示例，我们在分子信标中引入了远程变构位点，分子信标是用于检测特定核酸序列的光学传感器。抑制剂和激活剂与这些位点的结合使传感器的目标亲和力得以合理调节-从而使传感器的有用动态范围扩展了 3 个数量级。这种方法的便利性表明，人群转移机制可能成为引入变构调节的有用方法，可用于生物传感器、“智能”生物材料和其他人工生物技术。
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