Connecting Artificial Proteolytic and Electrochemical Signaling Systems with Caged Messenger Peptides

• DOI: 10.1021/acssensors.1c00845
• Publication Date: 2021-10-14T01:07:41Z
• Authors: Paolo Bollella; Selvakumar Edward...; Zhong Guo; Claudia E. Vickers; Jason Whitfield; Patricia Walden; Artem Melman; Kirill Alexandrov; Evgeny Katz
• Keywords: Proteolysis; Proteolytic enzymes

Enzymatic polypeptide proteolysis is a widespread and powerful biological control mechanism. Over the last few years, substantial progress has been made in creating artificial proteolytic systems where an input of choice modulates protease activity thereby its substrates. However, all developed so far have relied on direct cleavage their effectors. Here, we propose new concept biosensors with tunable uncage signaling peptide, which can then transmit signal to allosteric protein reporter. We demonstrate that both cage regulatory domain reporter be constructed from same peptide-binding domain, such as calmodulin. To this concept, rapamycin biosensor demonstrated quantitative actuation fluorescent, luminescent, electrochemical reporters. Using latter, sensitive bioelectrodes detect messenger peptide release quantitatively convert recognition event into electric current. discuss application for construction vitro sensory arrays vivo circuits.