The discovery and development of target probe of proteins

As one of the most abundant biological macromolecules, protein is the main performer of biological function and plays a key role in all kinds of life activities. Scientists have been exploring the application of protein manipulation tools in the living environment through recombinant human proteins in order to achieve the goal of protein structure and function of in-depth study, which has become one of the frontiers of the field of chemical biology. Many research groups in China have realized the specific activation of proteins through chemical decoupling technology, two-photon and near-infrared control technology and targeted small molecule probes and studied the molecular mechanism of cell signal transduction process.

In the field of chemical decoupling technology, Chen Peng's group put forward a new strategy of rational design of small molecule activator by combining non-natural amino acid fixed-point insertion technology and biological orthogonal "chemical decoupling" reaction. For example, protein kinase-mediated phosphorylation is a key process in cellular signal transduction and has a major influence on most physiological activities. However, the molecular mechanism of many kinases under normal physiological and pathological conditions is unclear. The use of small molecule activators can be used in kinase signaling studies to obtain new information. "We activate the 'effector protein OspF' in living cells and found that this protein causes 'phosphorylated Erk protein' in the nucleus to undergo a 'nuclear transport' mediated by irreversible dephosphorylation," said Chen.

In recent years, protein light-control technology has become another powerful tool to study cell signal transduction. Compared with the UV-excited probe, the two-photon-excited probe can greatly reduce the cytotoxicity and has broad application prospects. Liu Lei group from Tsinghua University took protein synthesis as the core technology to develop targeted immune protein light-control probe and made use of newly-developed protein probe of the immune cells in precise space-time stimulation of directional movement. This probe will provide an ideal molecular tool for understanding and controlling cell localization and localization-related cellular life activities in living tissue. Chen Xing group from Peking University has developed the use of near-infrared light activation and regulation of cell signal transduction pathway of the new method.

Yang Yi, a research group of East China University of Science and Technology used the natural photosensors to construct a light-controlled gene expression system for the targeted protein production and degradation. In the experiment, the researchers used the light to the live cells or the living animal protein production level carries precise control on time and space, successfully controlling the production of the insulin in diabetes mellitus body and the blood sugar concentration.

Li Yanmei research group from Tsinghua University used adjustable protein degradation strategy to achieve the target protein level within the cell decreased in order to achieve the purpose of reducing its activity. The researchers focused on the phenomenon of abnormal "non-enzymatic protein Tau" in the brain of Alzheimer's disease and used the "recognition-cutting" strategy to control the content of these proteins in cells. Flarebio provides you with good-quality recombinant proteins including recombinant TLR2 at good prices.