Department of Chemistry, Louisiana State University , Baton Rouge, Louisiana 70803, United States.
J Am Chem Soc. 2014 Jun 25;136(25):8843-6. doi: 10.1021/ja501859w. Epub 2014 Jun 12.
Availability of strategies for molecular biosensing over a finely adjustable dynamic range is essential for understanding and controlling vital biological processes. Herein we report design principles of highly responsive pH sensors based on a DNA i-motif where both response sensitivity and transition midpoint can be tuned with high precision over the physiologically relevant pH interval. The tuning is accomplished via rational manipulations of an i-motif structure as well as incorporation of allosteric control elements. This strategy delivers molecular sensing systems with a transition midpoint tunable with 0.1 pH units precision and with a total response range as narrow as 0.2 pH units which can be adjusted to a variety of outputs (e.g., fluorescent readout). The potential of the presented approach is not limited by pH sensing but may extend toward manipulation of other quadruplex based structures or the development of ultraresponsive elements for artificial molecular machines and signaling systems.
在可精细调节的动态范围内提供分子生物传感策略对于理解和控制重要的生物过程至关重要。在此，我们报告了基于 DNA i-motif 的高响应 pH 传感器的设计原理，其中响应灵敏度和转变中点都可以在生理相关的 pH 范围内进行高精度调节。通过合理操纵 i-motif 结构以及引入别构控制元件来实现调节。该策略提供了分子传感系统，其转变中点可通过 0.1 pH 单位的精度进行调节，总响应范围窄至 0.2 pH 单位，可以调整为各种输出（例如荧光读出）。所提出的方法的潜力不仅限于 pH 传感，还可以扩展到其他四链体结构的操作或用于人工分子机器和信号系统的超响应元件的开发。
