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Chapter 1 Project Overview
1.1 Introduction
1.1.1 Arrangement and Comprehensive Integration
1.1.2 Interdisciplinary Cooperation
1.2 Research Overview
1.2.1 Overall Scientific Objectives
1.2.2 Key Scientific Issues
1.3 Significant Progress
1.3.1 Development of Small Molecule Probes ()300 Types) Based on Natural Products and Chemical and Biological Synthesis, and Discovery of Multiple ¡°Star Molecules
1.3.2 Development of Special Techniques and Frontier Analysis Methods of Chemical Biology Including the Bioorthogonal
Reaction and Single Molecule/Cell Detection
1.3.3 Elucidation of Key Signal Transduction Processes Including Cell Reprogramming, Glycolipid Metabolism, Cell Apoptosis, and
Wnt Signaling Pathways
1.3.4 Discovery of New Targets and Lead Compounds for Infectious, Metabolic, and Inflammatory Diseases, and Tumors
Chapter 2 Domestic and Foreign Research
2.1 Thriving of "Small-Molecule Intervention"
2.1.1 Diversity-Oriented Functional Compound Library
2.1.2 Early Exploration of Drug Discovery
2.2 Extensive Introduction of Biomolecular "Unnatural Analogues"
2.3 Extension of Exogenous Chemical Reactions to Living Systems
2.4 Efficient Chemical Synthesis of Biomacromolecules
2.5 Rapid Advances in Biological Detection Technologies
2.5.1 Bioimaging
2.5.2 Chemical Proteomics
2.5.3 Chemical Modifications of Nucleic Acids and Next-Generation Sequencing Technologies
2.5.4 Single Molecule Detection and Single Cell Analysis
2.6 Research on Biology-Directed Scientific Problems
Chapter 3 Major Research Achievements
3.1 Specific Regulation Technologies Targeting Proteins in Cellular Signal Transduction
3.1.1 New Technology Targeting Protein Kinase¡ªChemical Decaging
3.1.2 Light-Controlled Protein Probes Targeting Immune Cell Activation
3.1.3 Near-Infrared Light-Controlled Activation Targeting Cell Surface Receptors
3.1.4 Probes for the Generation and Degradation of Target Proteins
3.1.5 Ultra-Bright Photoactivatable Fluorescent Proteins
3.2 Investigations on the Roles of Nucleic Acids in Signal Transduction Processes Utilizing Small Chemical Probes
3.2.1 Studies on Signal Transduction Regulation Based on the Ligands of Quadruplex Nucleic Acids
3.2.2 Regulation Based on Modified Nucleic Acids and Noncanonical Nucleic Acid Structures
3.3 Revealing New Mechanisms of Cell Signal Transduction Processes with Active Natural Products as Probes
3.3.1 Discovery of Anti-Leukemic Active Compounds
3.3.2 Discovery of Adenanthin T Discovery of Adenanthin Targeting Peroxiredoxin I /¢ò
3.3.3 Signaling Pathways of Adenanthin Targeting Prx I / II to Induce AML Cell Differentiation
3.3.4 Discovery of New Compounds Inducing AML Cell Differentiation with Prx I as a Target
3.3.5 Extended Research on the Antitumor Effect of Adenanthin Targeting Prx I /¢ò
3.3.6 Regulation Mechanism of Wnt Signaling and Apoptosis Pathways by the Natural Product Diterpenoid S-
3.4 Investigations on Regulation Mechanisms of Glycolipid Metabolism via Small-Molecule Probes
3.4.1 Cholesterol Transport Through Lysosome-Peroxisome Membrane Contacts
3.4.2 Negative Regulation Mechanism of Cholesterol Synthesis Metabolism and Molecular Pathway of Intestinal Absorption of
Cholesterol
3.4.3 Exploration of Endoplasmic Reticulum Stress and Glycolipid Metabolism and Discovery of Important Regulatory Active
Small Molecules
3.5 Discovery and Validation of Drug Targets and Lead Compounds Based on Signal Transduction Processes
3.5.1 Discovery and Functional Validation of Targets and Design of Lead Compounds for Antitumor Drugs
3.5.2 Discovery and Validation of a New Target for Anti-Inflammatory Drugs
3.5.3 Studies of Targets in the RNA Epigenetic Signal Transduction Pathways
3.5.4 Discovery of New Sites and Functions of the Drug Target