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Published on: November 10, 2016
Interstrand cross-link formation in duplex and triplex DNA by modified pyrimidines
Xiaohua Peng1, In Seok Hong, Hong Li
1Department of Chemistry, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA.
Journal of the American Chemical Society
|July 16, 2008
Summary
Phenylselenyl derivatives of thymidine and 5-methyl-2'-deoxycytidine create DNA interstrand cross-links (ICLs) through a specific chemical mechanism. These modified nucleosides offer versatile tools for DNA research and biotechnology applications.
Area of Science:
- Chemical Biology
- Molecular Biology
- Biotechnology
Background:
- DNA interstrand cross-links (ICLs) are significant in biological processes and biotechnology.
- Modified nucleosides can be used to create ICLs for research and therapeutic purposes.
Purpose of the Study:
- To investigate the mechanism and kinetics of ICL formation using phenylselenyl derivatives of thymidine (1) and 5-methyl-2 ahydrocytidine (5).
- To explore the utility of these modified nucleosides in duplex DNA and triplex forming oligonucleotides (TFOs).
Main Methods:
- Oxidation of phenylselenyl-substituted thymidine and deoxycytidine derivatives with NaIO4.
- Kinetic analysis of selenoxide rearrangement and methide intermediate formation.
- Incorporation of modified nucleosides into duplex DNA and TFOs.
Main Results:
- The rate-determining step for ICL formation occurs after methide intermediate generation.
- Cross-linking efficiency is sequence-dependent in duplex DNA and influenced by base pairing and mismatches.
- Modified deoxycytidine derivative (5) forms ICLs more efficiently than the thymidine derivative (1) in TFOs.
Conclusions:
- Phenylselenyl derivatives provide versatile tools for generating ICLs with tunable kinetics.
- These molecules serve as valuable mechanistic probes and biotechnological tools for DNA manipulation and study.
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