Squaramate-Modified Nucleotides and DNA for Specific Cross-Linking with Lysine-Containing Peptides and Proteins

Angew Chem Int Ed Engl. 2019 Sep 16;58(38):13345-13348. doi: 10.1002/anie.201906737. Epub 2019 Aug 13.

Abstract

Squaramate-linked 2'-deoxycytidine 5'-O-triphosphate was synthesized and found to be good substrate for KOD XL DNA polymerase in primer extension or PCR synthesis of modified DNA. The resulting squaramate-linked DNA reacts with primary amines to form a stable diamide linkage. This reaction was used for bioconjugations of DNA with Cy5 and Lys-containing peptides. Squaramate-linked DNA formed covalent cross-links with histone proteins. This reactive nucleotide has potential for other bioconjugations of nucleic acids with amines, peptides or proteins without need of any external reagent.

Keywords: DNA; DNA polymerase; bioconjugation; cross-linking reactions; proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / metabolism*
  • Humans
  • Lysine / metabolism*
  • Nucleotides / metabolism*
  • Peptides / chemistry*
  • Proteins / chemistry*

Substances

  • Nucleotides
  • Peptides
  • Proteins
  • DNA
  • Lysine