Christopher Switzer
Professor

Physical Biochemistry Ph.D., Johns Hopkins University, 1987 Postdoctoral Fellow, University of Geneva, Switzerland, 1987 NSF Postdoctoral Fellow, ETH, Switzerland, 1988-1990 VOICE: 951-827-7266 EMAIL: christopher.switzer@ucr.edu

We are engaged in the design of nucleic acids with new functional properties, and in attempts to discover possible ancient functional roles of this molecular class. We are also interested in developing new methodology relating to the chemistry of nucleic acids.

Nucleic Acid Design:
One project in this area involves the synthesis of oligonucleotide analogs, intended: (1) to be capable of diffusion into cells, (2) to be resistant to cellular enzymes that degrade nucleic acids, and (3) to have a high affinity for their complementary sequences in RNA messages. Oligonucleotides of this type are potentially useful in controlling the expression of genes both in vitro and in vivo. We plan to conduct experiments with these oligonucleotides that model aspects of an encounter with a cell. In addition, by virtue of their modified nature, these oligonucleotides may also be used to investigate how certain molecular features affect the association of nucleic acids with one another. We are interested in probing such effects using physical organic methods. Other projects in this area address a variety of hypotheses concerning nucleic acid structure.

Search for Ancient Functional Roles of Nucleic Acids:
RNA or RNA-like polymers are candidates for the first biotic self-replicating molecules. Support for this notion comes from known abilities of natural nucleic acids to participate in non-enzymatic, template-directed oligomerizations and to serve as catalysts. Currently we are synthesizing and evaluating non-standard nucleotide oligomers whose properties may be relevant to the origins of life. One such oligomer we have recently prepared possesses a non-standard 2',5'-internucleotide linkage in place of the natural 3',5'-linkage. We have found 2',5'-DNA capable of associating to form double-stranded and triple-stranded complexes. Investigations of these and related oligomers are ongoing.

SELECTED PUBLICATIONS
Prakash, T.P., Roberts, C. and Switzer, C. Activity of 2',5'-linked RNA in the template-directed oligomerization of mononucleotides. Angewandte Chemie Int. Ed. Engl., In Press.

Roberts, C., Bandaru, R. and Switzer, C. A theoretical and experimental study of iso-C and iso-G: base pairing in an expanded genetic system. J. Am Chem. Soc. 119:4640-49 (1997).

Strauss, J.K., Roberts, C., Nelson, M.G., Switzer, C. and Maher, L.J. DNA bending by tethered cations. Proc. Natl. Acad. Sci., U.S.A. 93:9515-9520 (1996).

Prakash, T.P., Jung, K.-E. and Switzer, C. RNA recognition by the 2'-structural isomer of DNA. Chem. Comm. 1793-1794 (1996).

Roberts, C., Bandaru, R.; Switzer, C. Synthesis of oligonucleotides bearing the non-standard bases iso-C and iso-G. Comparison of iso-Ciso-G, CG and UA base-pair stabilities in RNA/DNA duplexes. Tetrahedron Lett. 36:3601-3604 (1995).

Hashimoto, H., Nelson, M.G. and Switzer, C. Zwitterionic DNA. J. Am. Chem. Soc. 115:7128-7134 (1993).