Synergy of Two Highly Specific Biomolecular Recognition Events: Aligning an AT-Hook Peptide in DNA Minor Grooves via Covalent Conjugation to 2'-Amino-LNA

Maria Ejlersen, Niels Johan Christensen, Kasper K Sørensen, Knud J Jensen, Jesper Wengel, Chenguang Lou

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Abstract

Two highly specific biomolecular recognition events, nucleic acid duplex hybridization and DNA-peptide recognition in the minor groove, were coalesced in a miniature ensemble for the first time by covalently attaching a natural AT-hook peptide motif to nucleic acid duplexes via a 2'-amino-LNA scaffold. A combination of molecular dynamics simulations and ultraviolet thermal denaturation studies revealed high sequence-specific affinity of the peptide-oligonucleotide conjugates (POCs) when binding to complementary DNA strands, leveraging the bioinformation encrypted in the minor groove of DNA duplexes. The significant cooperative DNA duplex stabilization may pave the way toward further development of POCs with enhanced affinity and selectivity toward target sequences carrying peptide-binding genetic islands.

Original languageEnglish
JournalBioconjugate Chemistry
Volume29
Issue number4
Pages (from-to)1025–1029
ISSN1043-1802
DOIs
Publication statusPublished - 2018

Keywords

  • Binding Sites
  • DNA/chemistry
  • Hydrogen Bonding
  • Molecular Dynamics Simulation
  • Nucleic Acid Conformation
  • Nucleic Acid Heteroduplexes/chemistry
  • Oligonucleotides/chemistry
  • Peptides/chemistry
  • Proof of Concept Study
  • Protein Conformation

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