Abstract

In this application the PI proposes to continue studies on topologically constrained oligonucleotides which are designed to bind to RNA or DNA. These oligonucleotides are capable of forming triple-stranded complexes with targeted nucleic acids and include circular oligonucleotides, stem- loop oligonucleotides, purine hairpin oligonucleotides, and cross-linked and bicyclic oligonucleotides.
The specific aims of the proposal include: (1) Exploration of novel approaches to targeting structured nucleic acids; (2) Optimization of modifications for enhancing RNA-binding properties; (3) Evaluation of new synthetic approaches to topologically modified oligonucleotides; and (4) Collaborative testing of these new molecular strategies in HIV-infected cells. The long term objectives of the studies are to optimize the performance of synthetic oligonucleotides and to test them in applications directly related to HIV-1 infection. This includes both medical diagnostic and potentially therapeutic applications.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
7R01GM046625-10
Application #
6152687
Study Section
AIDS and Related Research Study Section 4 (ARRD)
Project Start
1991-07-01
Project End
2000-07-31
Budget Start
1999-10-03
Budget End
2000-07-31
Support Year
10
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Stanford University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305

  Publications

Mohsen, Michael G; Kool, Eric T (2016) The Discovery of Rolling Circle Amplification and Rolling Circle Transcription. Acc Chem Res 49:2540-2550
Ohmichi, T; Kool, E T (2000) The virtues of self-binding: high sequence specificity for RNA cleavage by self-processed hammerhead ribozymes. Nucleic Acids Res 28:776-83
Xu, Y; Kool, E T (1999) High sequence fidelity in a non-enzymatic DNA autoligation reaction. Nucleic Acids Res 27:875-81
Xu, Y; Kool, E T (1998) Chemical and enzymatic properties of bridging 5'-S-phosphorothioester linkages in DNA. Nucleic Acids Res 26:3159-64
Wang, S; Xu, Y; Kool, E T (1997) Recognition of RNA by triplex formation: divergent effects of pyrimidine C-5 methylation. Bioorg Med Chem 5:1043-50
Kool, E T (1996) Circular oligonucleotides: new concepts in oligonucleotide design. Annu Rev Biophys Biomol Struct 25:1-28
Wang, S; Friedman, A E; Kool, E T (1995) Origins of high sequence selectivity: a stopped-flow kinetics study of DNA/RNA hybridization by duplex- and triplex-forming oligonucleotides. Biochemistry 34:9774-84
Wang, S; Kool, E T (1994) Circular RNA oligonucleotides. Synthesis, nucleic acid binding properties, and a comparison with circular DNAs. Nucleic Acids Res 22:2326-33
Booher, M A; Wang, S; Kool, E T (1994) Base pairing and steric interactions between pyrimidine strand bridging loops and the purine strand in DNA pyrimidine.purine.pyrimidine triplexes. Biochemistry 33:4645-51
Wang, S; Booher, M A; Kool, E T (1994) Stabilities of nucleotide loops bridging the pyrimidine strands in DNA pyrimidine.purine.pyrimidine triplexes: special stability of the CTTTG loop. Biochemistry 33:4639-44

Showing the most recent 10 out of 11 publications