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 Kildegaard Sørensen; Knud Jørgen Jensen; Jesper Wengel; Chenguang Lou

doi:10.1021/acs.bioconjchem.8b00101

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 Kildegaard Sørensen, Knud Jørgen Jensen, Jesper Wengel, Chenguang Lou

Department of Chemistry

4 Citations (Scopus)

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 language	English
Journal	Bioconjugate Chemistry
Volume	29
Pages (from-to)	1025-1029
Number of pages	5
ISSN	1043-1802
DOIs	https://doi.org/10.1021/acs.bioconjchem.8b00101
Publication status	Published - 18 Apr 2018

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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 Kildegaard et al.

In: Bioconjugate Chemistry, Vol. 29, 18.04.2018, p. 1025-1029.

Research output: Contribution to journal › Journal article › Research › peer-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.",

author = "Maria Ejlersen and Christensen, {Niels Johan} and S{\o}rensen, {Kasper Kildegaard} and Jensen, {Knud J{\o}rgen} and Jesper Wengel and Chenguang Lou",

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doi = "10.1021/acs.bioconjchem.8b00101",

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AU - Ejlersen, Maria

AU - Christensen, Niels Johan

AU - Sørensen, Kasper Kildegaard

AU - Jensen, Knud Jørgen

AU - Wengel, Jesper

AU - Lou, Chenguang

PY - 2018/4/18

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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.

U2 - 10.1021/acs.bioconjchem.8b00101

DO - 10.1021/acs.bioconjchem.8b00101

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SN - 1043-1802

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JO - Bioconjugate Chemistry

JF - Bioconjugate Chemistry

ER -

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

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