Bioconjugation of Oligodeoxynucleotides Carrying 1,4-Dicarbonyl Groups via Reductive Amination with Lysine Residues

Bo Yang, Akiko Jinnouchi, Kazuteru Usui, Tsutomu Katayama, Masayuki Fujii, Hiroshi Suemune, Mariko Aso

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

We evaluated the efficacy of bioconjugation of oligodeoxynucleotides (ODNs) containing 1,4-dicarbonyl groups, a C4′-oxidized abasic site (OAS), and a newly designed 2′-methoxy analogue, via reductive amination with lysine residues. Dicarbonyls, aldehyde and ketone at C1- and C4-positions of deoxyribose in the ring-opened form of OAS allowed efficient reaction with amines. Kinetic studies indicated that reductive amination of OAS-containing ODNs with a proximal amine on the complementary strand proceeded 10 times faster than the corresponding reaction of an ODN containing an abasic site with C1-aldehyde. Efficient reductive amination between the DNA-binding domain of Escherichia coli DnaA protein and ODNs carrying OAS in the DnaA-binding sequence proceeded at the lysine residue in proximity to the phosphate group at the 5′-position of the OAS, in contrast to unsuccessful conjugation with abasic site ODNs, even though they have similar aldehydes. Theoretical calculation indicated that the C1-aldehyde of OAS was more accessible to the target lysine than that of the abasic site. These results demonstrate the potential utility of cross-linking strategies that use dicarbonyl-containing ODNs for the study of protein-nucleic acid interactions. Conjugation with a lysine-containing peptide that lacked specific affinity for ODN was also successful, further highlighting the advantages of 1,4-dicarbonyls.

Original languageEnglish
Pages (from-to)1830-1838
Number of pages9
JournalBioconjugate Chemistry
Volume26
Issue number8
DOIs
Publication statusPublished - Aug 19 2015

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Amination
Oligodeoxyribonucleotides
Lysine
Aldehydes
Amines
Deoxyribose
Proteins
Escherichia coli Proteins
Nucleic acids
Ketones
Escherichia coli
Nucleic Acids
Peptides
Phosphates
DNA
Kinetics

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

Cite this

Bioconjugation of Oligodeoxynucleotides Carrying 1,4-Dicarbonyl Groups via Reductive Amination with Lysine Residues. / Yang, Bo; Jinnouchi, Akiko; Usui, Kazuteru; Katayama, Tsutomu; Fujii, Masayuki; Suemune, Hiroshi; Aso, Mariko.

In: Bioconjugate Chemistry, Vol. 26, No. 8, 19.08.2015, p. 1830-1838.

Research output: Contribution to journalArticle

Yang, Bo ; Jinnouchi, Akiko ; Usui, Kazuteru ; Katayama, Tsutomu ; Fujii, Masayuki ; Suemune, Hiroshi ; Aso, Mariko. / Bioconjugation of Oligodeoxynucleotides Carrying 1,4-Dicarbonyl Groups via Reductive Amination with Lysine Residues. In: Bioconjugate Chemistry. 2015 ; Vol. 26, No. 8. pp. 1830-1838.
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