摘要 | 第3-6页 |
abstract | 第6-7页 |
Chapter 1 Introduction | 第10-28页 |
1.1 The source and significance of the research project | 第10-17页 |
1.1.1 The introduction of drug metabolism | 第10页 |
1.1.2 The introduction of Cytochrome P450s | 第10-14页 |
1.1.3 The introduction of doping drugs | 第14-15页 |
1.1.4 The introduction of CYP3A family enzymes | 第15-17页 |
1.2 The progress of the research project all over the world | 第17-19页 |
1.2.1 The research progress of doping drugs | 第17-18页 |
1.2.2 The research progress of CYP3A family | 第18-19页 |
1.3 The objective of the research project | 第19-28页 |
1.3.1 The objective of studying doping drugs | 第19-24页 |
1.3.2 The objective of CYP3A family enzymes investigation | 第24-28页 |
Chapter 2 Materials and Methods | 第28-40页 |
2.1 P450 dependent metabolism of doping compound | 第28-34页 |
2.1.1 Wagner-Meerwein rearrangement | 第28页 |
2.1.2 Whole cell biotransformation | 第28-30页 |
2.1.3 Fermentation | 第30-31页 |
2.1.4 Biotransformation with permeabilized fission yeast cells (enzyme bags) | 第31-33页 |
2.1.5 Metabolite purification and structure characterization | 第33-34页 |
2.2 Extended activity characterization of CYP3A enzymes | 第34-40页 |
2.2.1 Significant CYP activity demonstration | 第34-37页 |
2.2.2 Percentage inhibition values determination | 第37-40页 |
Chapter 3 Results | 第40-56页 |
3.1 P450 dependent metabolism of doping compound | 第40-50页 |
3.1.1 Chemical synthesis and cytochrome P450 testing | 第40-42页 |
3.1.2 Substrate docking | 第42-44页 |
3.1.3 Large scale metabolite production by fermentation | 第44-46页 |
3.1.4 Product purification and structure characterization | 第46-49页 |
3.1.5 Urine analysis and proof of relevance | 第49-50页 |
3.2 Extended activity characterization of CYP3A enzymes | 第50-56页 |
3.2.1 Significant activity demonstration of CYP3A enzymes | 第50-54页 |
3.2.2 Percentage inhibition values determination of CYP3A enzymes | 第54-56页 |
Chapter 4 Discussion | 第56-60页 |
4.1 Discussion of P450 dependent metabolism of doping compound | 第56-57页 |
4.2 Discussion of extended activity characterization of CYP3A enzymes | 第57-60页 |
Chapter 5 Conclusions and future prospects | 第60-66页 |
5.1 Conclusions of this research project | 第60-62页 |
5.1.1 Conclusion of P450 dependent metabolism of doping compound | 第60-61页 |
5.1.2 Conclusion of extended activity characterization of CYP3A enzymes | 第61-62页 |
5.2 Future prospects of this research project | 第62-66页 |
5.2.1 Future prospect of P450 dependent metabolism of doping compound | 第62-63页 |
5.2.2 Future prospect of extended activity characterization of CYP3A enzymes | 第63-66页 |
References | 第66-74页 |
Appendices | 第74-76页 |
Notes on publications and participation in scientific research | 第76-78页 |
Acknowledgements | 第78页 |