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Site-specific gene point mutations can be introduced using oligonucleotides with analog bases that generate covalently bonded adducts on specific bases in a DNA sequence. Depending on the nature of the adduct formed, a point mutation can be induced at the binding site during transcription. In addition to being a useful research tool, this mutagenesis approach is offers therapeutic potential, for example, to correct gene abnormalities or inhibit reproduction of pathogenic organisms. We have developed novel thionucleoside-S-nitrosyl derivatives, oligonucleotides capable of specifically transferring a nitrosyl group to a targeted nucleotide, and a method to chemically induce specific point mutations in a target gene sequence. Oligonucleotides containing novel nitrosyl derivatives are synthesized by nitrosylating nucleotides that have thiocarbonyl substitutions of their carbonyl group Oligonucleotides containing these modified nucleotides are able to transfer the nitrosyl group in a base-specific manner when hybridized to a specific sequence.
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