This proposal brings together a number of efforts in the lab centered on nucleic acid structure, function and manipulation. All these projects are focused on generating nucleic acids and nucleic acid complexes with novel properties by a combination of rational design and molecular evolution. In particular we are attempting to design and characterize novel DNAs with altered base-pairing interactions based on metal complexation. Ultimately, our hope is to be able to enzymatically synthesize such pairs to use in applications for information storage and the in vitro evolution of nucleic acids with novel functions. At a higher level of structure, we will attempt to generate circular, folded RNAs that are capable as acting as viruses- are infective, can be replicated in vivo, and can modulate cellular function. Such molecules would find applications in cell-based functional genomics and possibly therapeutic applications. Finally, at the level of selective protein-nucleic acid complexes, we are attempting to generate a series of sequence specific recombinases that can be used for cloning experiments, in cellular genetic disruption/insertion experiments, or possibly transgenic animal experiments. In addition to the applications described above, these experiments will likely provide new insights into nucleic acid structure, function and recognition.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM064403-03
Application #
6783344
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Program Officer
Lograsso, Philip
Project Start
2002-08-01
Project End
2006-07-31
Budget Start
2004-08-01
Budget End
2005-07-31
Support Year
3
Fiscal Year
2004
Total Cost
$351,880
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Zimmermann, Nicole; Meggers, Eric; Schultz, Peter G (2004) A second-generation copper(II)-mediated metallo-DNA-base pair. Bioorg Chem 32:13-25
Lin, Qing; Barbas 3rd, Carlos F; Schultz, Peter G (2003) Small-molecule switches for zinc finger transcription factors. J Am Chem Soc 125:612-3