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

Research output: Contribution to journalLetterResearchpeer-review

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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

Fingerprint

AT-Hook Motifs
Hooks
Peptides
DNA
Oligonucleotides
Nucleic acids
Nucleic Acids
Denaturation
Molecular Dynamics Simulation
Scaffolds
Molecular dynamics
Stabilization
Complementary DNA
amino-LNA
Computer simulation

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

Cite this

@article{ccdce9860edf443cacb8d05ae0b58a7f,
title = "Synergy of Two Highly Specific Biomolecular Recognition Events: Aligning an AT-Hook Peptide in DNA Minor Grooves via Covalent Conjugation to 2'-Amino-LNA",
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.",
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",
author = "Maria Ejlersen and Christensen, {Niels Johan} and S{\o}rensen, {Kasper K} and Jensen, {Knud J} and Jesper Wengel and Chenguang Lou",
year = "2018",
doi = "10.1021/acs.bioconjchem.8b00101",
language = "English",
volume = "29",
pages = "1025–1029",
journal = "Bioconjugate Chemistry",
issn = "1043-1802",
publisher = "American Chemical Society",
number = "4",

}

Synergy of Two Highly Specific Biomolecular Recognition Events : Aligning an AT-Hook Peptide in DNA Minor Grooves via Covalent Conjugation to 2'-Amino-LNA. / Ejlersen, Maria; Christensen, Niels Johan; Sørensen, Kasper K; Jensen, Knud J; Wengel, Jesper; Lou, Chenguang.

In: Bioconjugate Chemistry, Vol. 29, No. 4, 2018, p. 1025–1029.

Research output: Contribution to journalLetterResearchpeer-review

TY - JOUR

T1 - Synergy of Two Highly Specific Biomolecular Recognition Events

T2 - Aligning an AT-Hook Peptide in DNA Minor Grooves via Covalent Conjugation to 2'-Amino-LNA

AU - Ejlersen, Maria

AU - Christensen, Niels Johan

AU - Sørensen, Kasper K

AU - Jensen, Knud J

AU - Wengel, Jesper

AU - Lou, Chenguang

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Binding Sites

KW - DNA/chemistry

KW - Hydrogen Bonding

KW - Molecular Dynamics Simulation

KW - Nucleic Acid Conformation

KW - Nucleic Acid Heteroduplexes/chemistry

KW - Oligonucleotides/chemistry

KW - Peptides/chemistry

KW - Proof of Concept Study

KW - Protein Conformation

U2 - 10.1021/acs.bioconjchem.8b00101

DO - 10.1021/acs.bioconjchem.8b00101

M3 - Letter

C2 - 29505242

VL - 29

SP - 1025

EP - 1029

JO - Bioconjugate Chemistry

JF - Bioconjugate Chemistry

SN - 1043-1802

IS - 4

ER -