The Chemical Modification of Nucleic Acids

Psoralen photochemistry is specific for nucleic acids and is better understood at the molecular level than are all other methods of chemical modification of nucleic acids. These compounds are used both for in vivo structure analysis and for photochemotherapy since they easily penetrate both cells and virus particles. Apparently, natural selection has selected for membrane and virus penetrability during the evolution of these natural products. Most cells are unaffected by relatively high concentrations of psoralens in the absence of ultraviolet light, and the metabolites of the psoralens have thus far not created a problem. Finally, psoralens form both monoadduct and cross-links in nucleic acid helices, the yield of each being easily controlled by the conditions used during the photochemistry.

Download Full-text

Chemical Modification of Nucleic Acids and the Mutagenicity of Modified Bases, with Special Reference to Permanganate-and Bisulfite-Mediated Modifications

YAKUGAKU ZASSHI ◽

10.1248/yakushi1947.113.1_19 ◽

1993 ◽

Vol 113 (1) ◽

pp. 19-31 ◽

Cited By ~ 1

Author(s):

Hikoya HAYATSU

Keyword(s):

Nucleic Acids ◽

Chemical Modification ◽

Special Reference

Download Full-text

Thermodynamic and structural characterization of 2′-nitrogen-modified RNA duplexes

Nucleic Acids Research ◽

10.1093/nar/gkh658 ◽

2004 ◽

Vol 32 (11) ◽

pp. 3446-3455 ◽

Cited By ~ 12

Author(s):

John W. Pham ◽

Ishwar Radhakrishnan ◽

Erik J. Sontheimer

Keyword(s):

Molecular Modeling ◽

Nmr Spectroscopy ◽

Nucleic Acids ◽

Chemical Modification ◽

Structural Characterization ◽

Cross Linking ◽

Base Pairing ◽

Alkyl Groups ◽

Rna Duplexes

Abstract 2′-aminonucleosides are commonly used as sites of post-synthetic chemical modification within nucleic acids. As part of a larger cross-linking strategy, we appended alkyl groups onto the N2′ position of 2′-amino-modified RNAs via 2′-ureido and 2′-amido linkages. We have characterized the thermodynamics of 2′-amino, 2′-alkylamido and 2′-alkylureido-modified RNA duplexes and show that 2′-ureido-modified RNAs are significantly more stable than analogous 2′-amido-modified RNAs. Using NMR spectroscopy and NMR-based molecular modeling of 2′-modified RNA duplexes, we examined the effects that 2′-nitrogen modifications have on RNA helices. Our data suggest that the 2′-ureido group forms a specific intra-nucleoside interaction that cannot occur within 2′-amido-modified helices. These results indicate that 2′-ureido modifications are superior to analogous 2′-amido ones for applications that require stable base pairing.

Download Full-text