Goggins Sean, Marsh Barrie J, Lubben Anneke T, Frost Christopher G
Department of Chemistry , University of Bath , Bath , BA2 7AY , UK . Email:
Atlas Genetics , Derby Court, Epsom Square, White Horse Business Park, Trowbridge , Wiltshire , BA14 0XG , UK . Email:
Chem Sci. 2015 Aug 1;6(8):4978-4985. doi: 10.1039/c5sc01588j. Epub 2015 Jun 15.
Signal transduction and signal amplification are both important mechanisms used within biological signalling pathways. Inspired by this process, we have developed a signal amplification methodology that utilises the selectivity and high activity of enzymes in combination with the robustness and generality of an organometallic catalyst, achieving a hybrid biological and synthetic catalyst cascade. A proligand enzyme substrate was designed to selectively self-immolate in the presence of the enzyme to release a ligand that can bind to a metal pre-catalyst and accelerate the rate of a transfer hydrogenation reaction. Enzyme-triggered catalytic signal amplification was then applied to a range of catalyst substrates demonstrating that signal amplification and signal transduction can both be achieved through this methodology.
信号转导和信号放大都是生物信号通路中使用的重要机制。受此过程启发,我们开发了一种信号放大方法,该方法利用酶的选择性和高活性,并结合有机金属催化剂的稳健性和通用性,实现了生物和合成催化剂的级联反应。设计了一种前配体酶底物,使其在酶存在下选择性地自裂解,以释放一种可与金属预催化剂结合并加速转移氢化反应速率的配体。然后将酶触发的催化信号放大应用于一系列催化剂底物,表明通过该方法可以实现信号放大和信号转导。