DNA-catalyzed lysine side chain modification

Benjamin M. Brandsen, Tania E. Velez, Amit Sachdeva, Nora A. Ibrahim, Scott K. Silverman

Research output: Contribution to journalArticle

Abstract

Catalyzing the covalent modification of aliphatic amino groups, such as the lysine (Lys) side chain, by nucleic acids has been challenging to achieve. Such catalysis will be valuable, for example, for the practical preparation of Lys-modified proteins. We previously reported the DNA-catalyzed modification of the tyrosine and serine hydroxy side chains, but Lys modification has been elusive. Herein, we show that increasing the reactivity of the electrophilic reaction partner by using 5-phosphorimidazolide (5-Imp) rather than 5-triphosphate (5-ppp) enables the DNA-catalyzed modification of Lys in a DNA-anchored peptide substrate. The DNA-catalyzed reaction of Lys with 5-Imp is observed in an architecture in which the nucleophile and electrophile are not preorganized. In contrast, previous efforts showed that catalysis was not observed when Lys and 5-ppp were used in a preorganized arrangement. Therefore, substrate reactivity is more important than preorganization in this context. These findings will assist ongoing efforts to identify DNA catalysts for reactions of protein substrates at lysine side chains.

Original languageEnglish (US)
Pages (from-to)9045-9050
Number of pages6
JournalAngewandte Chemie - International Edition
Volume53
Issue number34
DOIs
StatePublished - Aug 18 2014

Fingerprint

Lysine
DNA
Catalysis
Substrates
Proteins
Nucleophiles
Nucleic acids
Peptides
DNA-lysine adduct
Serine
Nucleic Acids
Tyrosine
Catalysts

Keywords

  • DNA
  • deoxyribozymes
  • in vitro selection
  • lysine modification
  • peptides

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

Cite this

DNA-catalyzed lysine side chain modification. / Brandsen, Benjamin M.; Velez, Tania E.; Sachdeva, Amit; Ibrahim, Nora A.; Silverman, Scott K.

In: Angewandte Chemie - International Edition, Vol. 53, No. 34, 18.08.2014, p. 9045-9050.

Research output: Contribution to journalArticle

Brandsen, BM, Velez, TE, Sachdeva, A, Ibrahim, NA & Silverman, SK 2014, 'DNA-catalyzed lysine side chain modification', Angewandte Chemie - International Edition, vol. 53, no. 34, pp. 9045-9050. https://doi.org/10.1002/anie.201404622
Brandsen, Benjamin M. ; Velez, Tania E. ; Sachdeva, Amit ; Ibrahim, Nora A. ; Silverman, Scott K. / DNA-catalyzed lysine side chain modification. In: Angewandte Chemie - International Edition. 2014 ; Vol. 53, No. 34. pp. 9045-9050.
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