Abstract
Replacement of the phosphodiester linkages of the polyanion DNA with guanidine linkers provides the polycation deoxynucleic guanidine (DNG). The synthesis of pentameric thymidyl DNA is provided. This polycationic DNG species binds with unprecedented affinity and with base-pair specificity to negatively charged poly(dA) to provide both double and triple helices. The dramatic stability of these hybrid structures is shown by their denaturation temperatures (Tm). For example, the double helix of the pentameric thymidyl DNG and poly(dA) does not dissociate in boiling water (ionic strength = 0.12), whereas the Tm for pentameric thymidyl DNA associated with poly(dA) is approximately 13 degrees C (ionic strength = 0.12). The effect of ionic strength on Tm for DNG complexes with DNA shows an opposite correlation compared with double-stranded DNA and is much more dramatic than for double-stranded DNA.
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- AKINRIMISI E. O., SANDER C., TS'O P. O. Properties of helical polycytidylic acid. Biochemistry. 1963 Mar-Apr;2:340–344. doi: 10.1021/bi00902a028. [DOI] [PubMed] [Google Scholar]
- Crooke S. T. Progress toward oligonucleotide therapeutics: pharmacodynamic properties. FASEB J. 1993 Apr 1;7(6):533–539. doi: 10.1096/fasebj.7.6.7682523. [DOI] [PubMed] [Google Scholar]
- Dempcy R. O., Almarsson O., Bruice T. C. Design and synthesis of deoxynucleic guanidine: a polycation analogue of DNA. Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):7864–7868. doi: 10.1073/pnas.91.17.7864. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fathi R., Huang Q., Syi J. L., Delaney W., Cook A. F. (Aminomethyl)phosphonate derivatives of oligonucleotides. Bioconjug Chem. 1994 Jan-Feb;5(1):47–57. doi: 10.1021/bc00025a007. [DOI] [PubMed] [Google Scholar]
- Glinski R. P., Khan M. S., Kalamas R. L., Sporn M. B. Nucleotide synthesis. IV. Phosphorylated 3'-amino-3'-deoxythymidine and 5'-amino-5'-deoxythymidine and derivatives. J Org Chem. 1973 Dec 14;38(25):4299–4305. doi: 10.1021/jo00964a020. [DOI] [PubMed] [Google Scholar]
- Riley M., Maling B. Physical and chemical characterization of two- and three-stranded adenine-thymine and adenine-uracil homopolymer complexes. J Mol Biol. 1966 Sep;20(2):359–389. doi: 10.1016/0022-2836(66)90069-6. [DOI] [PubMed] [Google Scholar]