The objective of this research is to develop efficient and rapid procedures for synthesizing polynucleotides and polynucleotide derivatives possessing any desired sequence of nucleotide units. Variations in the phosphite-triester method will be explored with syntheses conducted in solution and on silica gel supports. Attention will be given to new types of protecting groups and to anchoring groups that will enable one to release synthetic oligomeric nucleotides from the silica support as triester derivatives (which can subsequently be purified and coupled by the triester methodology to yield long chains). In addition to polymers possessing phosphodiester and phosphotriester backbones, polynucleotide derivatives with selectively designed, non-uniform backbones will be synthesized to generate substances with the recognition features of natural oligonucleotides but possessing unique properties with respect to stability, sensitivity to nucleases, and binding to complementary sequences.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37GM010265-27
Application #
3484093
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1977-03-01
Project End
1991-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
27
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
Schools of Arts and Sciences
DUNS #
City
Evanston
State
IL
Country
United States
Zip Code
60208
Letsinger, Robert L; Wu, Taifeng; Yang, Jye-Shane et al. (2008) DNA-templated formation and luminescence of diphenylacetylene dimeric and trimeric complexes. Photochem Photobiol Sci 7:854-9
Letsinger, R L (1993) Control of properties of oligonucleotides by chemical modifications. Nucleic Acids Symp Ser :1-2
Gryaznov, S M; Letsinger, R L (1992) Synthesis and properties of oligonucleotides containing aminodeoxythymidine units. Nucleic Acids Res 20:3403-9
Gryaznov, S M; Letsinger, R L (1992) Selective O-phosphitilation with nucleoside phosphoramidite reagents. Nucleic Acids Res 20:1879-82
Alul, R H; Singman, C N; Zhang, G R et al. (1991) Oxalyl-CPG: a labile support for synthesis of sensitive oligonucleotide derivatives. Nucleic Acids Res 19:1527-32
Letsinger, R L; Alul, R A; Farooqui, F et al. (1991) Synthesis and properties of modified oligonucleotides. Nucleic Acids Symp Ser :75-8
Letsinger, R L; Zhang, G R; Sun, D K et al. (1989) Cholesteryl-conjugated oligonucleotides: synthesis, properties, and activity as inhibitors of replication of human immunodeficiency virus in cell culture. Proc Natl Acad Sci U S A 86:6553-6
Letsinger, R L; Bach, S A; Eadie, J S (1986) Effects of pendant groups at phosphorus on binding properties of d-ApA analogues. Nucleic Acids Res 14:3487-99
Yamana, K; Letsinger, R L (1985) Synthesis and properties of oligonucleotides bearing a pendant pyrene group. Nucleic Acids Symp Ser :169-72