Synthesis of nucleoside and nucleotide conjugates of bile acids, and polymerase construction of bile acid-functionalized DNA.
Aqueous Sonogashira cross-coupling reactions of 5-iodopyrimidine or 7-iodo-7-deazaadenine nucleosides with bile acid-derived terminal acetylenes linked via an ester or amide tether gave the corresponding bile acid-nucleoside conjugates. Analogous reactions of halogenated nucleoside triphosphates gave directly bile acid-modified dNTPs. Enzymatic incorporation of these modified nucleotides to DNA was successfully performed using Phusion polymerase for primer extension. One of the dNTPs (dCTP bearing cholic acid) was also efficient for PCR amplification.
Ikonen
Satu
S
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead & IOCB Research Center, Flemingovo nam. 2, CZ-16610, Prague 6, Czech Republic.
Macícková-Cahová
Hana
H
Pohl
Radek
R
Sanda
Miloslav
M
Hocek
Michal
M
D001647:Bile Acids and Salts / Q000737:chemistry*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D009691:Nucleic Acid Denaturation; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry*; D009711:Nucleotides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D019710:Thermococcaceae / Q000201:enzymology*
D001647:Bile Acids and Salts; D009705:Nucleosides; D009711:Nucleotides; D004247:DNA; D004259:DNA-Directed DNA Polymerase