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

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 scaffo...

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Bibliographic Details
Published in:Bioconjugate chemistry 2018-04, Vol.29 (4), p.1025-1029
Main Authors: Ejlersen, Maria, Christensen, Niels Johan, Sørensen, Kasper K, Jensen, Knud J, Wengel, Jesper, Lou, Chenguang
Format: Article
Language:English
Subjects:
Affinity
Amino acids
Binding
Chemical bonds
Complementary DNA
Conjugation
Deoxyribonucleic acid
DNA
Gene sequencing
Grooves
Hybridization
Molecular biology
Molecular chains
Molecular dynamics
Next-generation sequencing
Nucleic acids
Oligonucleotides
Peptides
Recognition
Thermal denaturation
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Summary: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.
ISSN:1043-1802
1520-4812
DOI:10.1021/acs.bioconjchem.8b00101