2005 US Frontiers of Science Symposium

2005 US Frontiers of Science Symposium

Efforts to Expand the Genetic Alphabet

Floyd Romesberg, Scripps Research Institute

1. Introduction

2. Efforts to Expand the Genetic Alphabet

3. Efforts Toward Expansion of the Genetic Code

4. Requirements for a Third Base Pair

5. Unnatural Hydrophobic Nucleosides

6. Thermostability

7. Unnatural Hydrophobic Nucleosides

8. Thermostability

9. Polymerase-Mediated Replication (Kf)

10. The 7AI:ICS Base Pair

11. Optimization of Interbase Interactions

12. The PICS:PICS Self-Pair

13. The 3MN:3MN Self-Pair

14. NMR Structure of PICS:PICS Self-Pair

15. Unnatural Base Pairs

16. Polymerase-Mediated Replication

17. Extension Past Unnatural Base Pair

18. NMR Structure of PICS:PICS Self-Pair

19. Nucleobase Analogs with Reduced Aromatic Surface Area

20. Derivatized Phenyl Rings

21. 3FB Self-Pair Synthesis and Extension

22. Replication of DNA Containing dG:dC and 3FB Self-Pairs

23. NMR Characterization of 3FB Self-Pair

24. X-ray Crystal Structure of 3FB Self-Pair

25. Activity-Based Selection System

26. Description of Libraries

27. Optimization of PICS Self-Pair Replication

28. Q489H:F598I:I614F (P2) SF Mutant Extends PICS:PICS Self-Pair

29. P2 Synthesizes and Extends PICS Self-Pair in Contrast to Parental Enzyme, Which Does Neither

30. P2 Kinetic Characterization

31. Q489H:F598I:I614F (P2) SF Mutant

32. Acknowledgements

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