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Book of Abstracts: Albany 2005

category image Volume 22
No. 6
June 2005

Small Molecule Mediated Assembly of Nucleic Acids: Implications for the RNA World Hypothesis

The discovery of life?s origin is, in many ways, coupled to understanding the evolution of nucleic acids. In the contemporary world, proteins and nucleic acids are dependent upon each other for synthesis. However, the presence of protein enzymes on the primitive Earth has been deemed unlikely, at best. Such conjectures regarding early life have caused many researchers to ask how nucleic acids replicated and assembled before the appearance of protein enzymes. We have recently shown that proflavine, a small molecule that intercalates the bases of DNA and RNA, can significantly increase the template-directed coupling rate of short oligonucleotides (1). In this study we found that several proflavine molecules work together in a cooperative fashion to assemble the ligation-active complex. In essence, proflavine functions as a ?multimolecular enzyme? in an oligonucleotide ligation reaction. These results support the hypothesis that an intercalating molecule could have acted as a ?molecular midwife? that facilitated the synthesis and replication of information-containing polymers in the early stages of the RNA World (2). We have now investigated in greater detail what characteristics of small molecules and solution conditions are best for enhancing template-directed coupling of oligonucleotides. Our recent demonstration that non-Watson-Crick secondary structures can also be promoted by intercalation, such as a duplex with adenine·adenine base pairs (3, 4), suggests that information transfer in the presence of intercalating molecules may also be possible with non-canonical base pairs, or even with non-natural nucleotide bases. Progress towards intercalation-mediated chain growth using monononucleotides will also be discussed. Together, the work to be presented illustrates the great potential of intercalating molecules to facilitate non-enzymatic ligation of nucleic acids.

References and Footnotes
  1. Jain, S. S., Anet, F. A. L., Stahle, C. J., and Hud, N. V. Angew. Chem. Int. Ed. 43, 2004-2008 (2004).
  2. Hud, N. V. and Anet, F. A. L. J. Theor. Biol. 205, 543-562 (2000).
  3. Jain, S. S., Polak, M., and Hud, N. V. Nuc. Acids Res. 31, 4608-4615 (2003).
  4. Persil, O. Santai, C., Jain, S. S., and Hud, N. V. JACS 126, 8644-8645 (2004).

Swapan S. Jain*
Nicholas V. Hud

School of Chemistry and Biochemistry
Parker H. Petit Institute for Bioengineering and Biosciences
Georgia Institute of Technology
315 Ferst Drive, Atlanta, GA 30332

*Phone: 404-385-1166
Fax: 404-894-2295
Email: Jain@chemistry.gatech.edu