Oligonucleotides with 1,4-Dioxane-Based Nucleotide Monomers
摘要:
An epimeric mixture of H-phosphonates 5R and 5S has been synthesized in three steps from known secouridine 1. Separation of the epimers has been accomplished by RP-HPLC, allowing full characterization and incorporation of monomers X and Y into 9-mer oligonucleotides using H-phosphonates building blocks 5R and 5S, respectively. A single incorporation of either monomer X or monomer Y in the central position of a DNA 9-mer results in decreased thermal affinity toward both DNA and RNA complements (Delta T-m = -3.5 degrees C/-3.5 degrees C for monomer X and Delta T-m = -11.0 degrees C/-6.5 degrees C for monomer Y). CD measurements do not reveal major rearrangements of the duplexes formed, but molecular modeling suggests that local rearrangement of the sugar phosphate backbone and decreased base interactions with neighboring bases might be the origin of the decreased stability of duplexes.
Oligonucleotides with 1,4-Dioxane-Based Nucleotide Monomers
摘要:
An epimeric mixture of H-phosphonates 5R and 5S has been synthesized in three steps from known secouridine 1. Separation of the epimers has been accomplished by RP-HPLC, allowing full characterization and incorporation of monomers X and Y into 9-mer oligonucleotides using H-phosphonates building blocks 5R and 5S, respectively. A single incorporation of either monomer X or monomer Y in the central position of a DNA 9-mer results in decreased thermal affinity toward both DNA and RNA complements (Delta T-m = -3.5 degrees C/-3.5 degrees C for monomer X and Delta T-m = -11.0 degrees C/-6.5 degrees C for monomer Y). CD measurements do not reveal major rearrangements of the duplexes formed, but molecular modeling suggests that local rearrangement of the sugar phosphate backbone and decreased base interactions with neighboring bases might be the origin of the decreased stability of duplexes.
Oligonucleotides with 1,4-Dioxane-Based Nucleotide Monomers
作者:Andreas S. Madsen、Jesper Wengel
DOI:10.1021/jo300222q
日期:2012.4.20
An epimeric mixture of H-phosphonates 5R and 5S has been synthesized in three steps from known secouridine 1. Separation of the epimers has been accomplished by RP-HPLC, allowing full characterization and incorporation of monomers X and Y into 9-mer oligonucleotides using H-phosphonates building blocks 5R and 5S, respectively. A single incorporation of either monomer X or monomer Y in the central position of a DNA 9-mer results in decreased thermal affinity toward both DNA and RNA complements (Delta T-m = -3.5 degrees C/-3.5 degrees C for monomer X and Delta T-m = -11.0 degrees C/-6.5 degrees C for monomer Y). CD measurements do not reveal major rearrangements of the duplexes formed, but molecular modeling suggests that local rearrangement of the sugar phosphate backbone and decreased base interactions with neighboring bases might be the origin of the decreased stability of duplexes.