title: Synthesis of aldehyde-linked nucleotides and DNA and their bioconjugations with lysine and peptides through reductive amination.
abstract: 5-(5-Formylthienyl)-, 5-(4-formylphenyl)- and 5-(2-fluoro-5-formylphenyl)cytosine 2'-deoxyribonucleoside mono- (dC(R)MP) and triphosphates (dC(R)TP) were prepared by aqueous Suzuki-Miyaura cross-coupling of 5-iodocytosine nucleotides with the corresponding formylarylboronic acids. The dC(R)TPs were excellent substrates for DNA polymerases and were incorporated into DNA by primer extension or PCR. Reductive aminations of the model dC(R)MPs with lysine or lysine-containing tripeptide were studied and optimized. In aqueous phosphate buffer (pH 6.7) the yields of the reductive aminations with tripeptide III were up to 25 %. Bioconjugation of an aldehyde-containing DNA with a lysine-containing tripeptide was achieved through reductive amination in yields of up to 90 % in aqueous phosphate buffer.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences & IOCB Research Center, Flemingovo nam. 2, 16610 Prague 6, Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Raindlová
authors.forename: Radek
authors.initials: R
authors.lastname: Pohl
authors.forename: Michal
authors.initials: M
authors.lastname: Hocek
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D000586:Amination; D001483:Base Sequence; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D008239:Lysine / Q000737:chemistry*; D008956:Models, Chemical; D015394:Molecular Structure; D009711:Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D016133:Polymerase Chain Reaction
chemical_list: D000447:Aldehydes; D009711:Nucleotides; D010455:Peptides; D004259:DNA-Directed DNA Polymerase; D008239:Lysine