Peptide Series 12 || Star drug target protein-GPCR

Broadcast time and theme

Time: 19:00, Thursday, March 16, 2023

Topic: Star drug Target protein - GPCRS

Live Guest Introduction:

Li Yulei is an associate professor at the School of Pharmacy and Pharmaceutical Science, Shandong First Medical University. 2016-2019: Graduated from Ocean University of China, majoring in Pharmaceutical Chemistry, under the guidance of Professor Zhao Xia; 2019-2022: Postdoctoral research, Department of Chemistry, Tsinghua University, under the supervision of Professor Liu Lei; 2022-present: High-level talents, associate professor and master tutor of Shandong First Medical University. Research direction: Chemical synthesis of new technology strategies for the development of protein polypeptide drugs. Published more than 10 papers in journals such as Joumal of the American Chemical Society and ACS Chemical Biology as the first author, applied for 2 national invention patents as the first inventor, and authorized 1 national invention patent. He chaired the National Natural Science Foundation of China Youth Project, Tsinghua University-Peking University Life Joint Center Fund. Shandong First Medical University high-level talent program support projects.

Summary of report

G protein-coupled receptors (GPCRS) are the largest family of membrane proteins in the human genome, widely distributed in eukaryotic cell membranes, showing a seven-fold transmembrane helix, and are the target of more than 30% of current drugs, and the abnormal function of GPCRS leads to major diseases such as cardiovascular disease, neurodegenerative diseases and cancer. β₂- adrenergic receptor (β₂AR) is a classic model protein in the study of GPCR signal transduction and structure, and is an important drug target in respiratory system and asthma. Recently, it has been reported that C-terminal has multiple site phosphorylation and ubiquitination modifications, which mediate numerous physiological functions, including inhibiting β₂AR G protein coupling, activating β-arrestin to initiate β₂AR internalization, and recruiting ubiquitination ligase to regulate β₂AR degradation. Understanding the regulatory mechanisms of these posttranslational modifications in stabilizing receptor conformation, recruiting effector proteins, etc. will help to understand the disease-related abnormal mechanism of GPCR signaling, and will provide a basis for the development of drug molecules that selectively target the GPCR signaling pathway. Elucidation of how different posttranslational modifications regulate β₂AR function at the molecular level poses an important problem. Based on this, an important problem at present is how to obtain uniform C-terminal post-translational modified full-length β₂AR receptors and elucidate their biochemical properties.

In this report we will discuss:

1. Access and application of post-translational modified proteins;

2. The chemical synthesis process and related biochemical studies of full-length GPCR-β-O2 adrenergic receptor membrane protein with C-terminal phosphorylation/ubiquitination modification are introduced.