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

Kemisk Institut

4 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Bioconjugate Chemistry
Vol/bind	29
Sider (fra-til)	1025-1029
Antal sider	5
ISSN	1043-1802
DOI	https://doi.org/10.1021/acs.bioconjchem.8b00101
Status	Udgivet - 18 apr. 2018

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10.1021/acs.bioconjchem.8b00101

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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.

I: Bioconjugate Chemistry, Bind 29, 18.04.2018, s. 1025-1029.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › 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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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 Kildegaard

AU - Jensen, Knud Jørgen

AU - Wengel, Jesper

AU - Lou, Chenguang

PY - 2018/4/18

Y1 - 2018/4/18

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

M3 - Journal article

C2 - 29505242

SN - 1043-1802

VL - 29

SP - 1025

EP - 1029

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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