Synergy of Two Highly Specific Biomolecular Recognition Events:Aligning an AT-Hook Peptide in DNA Minor Grooves via Covalent Conjugation to 2'-Amino-LNA
| Autor: | Chenguang Lou, Knud J. Jensen, Niels Johan Christensen, Jesper Wengel, Kasper K. Sørensen, Maria Ejlersen |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Protein Conformation Oligonucleotides Biomedical Engineering Pharmaceutical Science Bioengineering Peptide Molecular Dynamics Simulation 010402 general chemistry Peptides/chemistry 01 natural sciences Proof of Concept Study 03 medical and health sciences chemistry.chemical_compound Protein structure Binding site Oligonucleotides/chemistry DNA/chemistry Pharmacology chemistry.chemical_classification Binding Sites Oligonucleotide Organic Chemistry Nucleic Acid Heteroduplexes Hydrogen Bonding DNA 0104 chemical sciences 030104 developmental biology chemistry Duplex (building) Biophysics Nucleic acid Nucleic Acid Conformation Nucleic Acid Heteroduplexes/chemistry Peptides Biotechnology |
| Zdroj: | Ejlersen, M, Christensen, N J, Sørensen, K K, Jensen, K J, Wengel, J & Lou, C 2018, ' Synergy of Two Highly Specific Biomolecular Recognition Events : Aligning an AT-Hook Peptide in DNA Minor Grooves via Covalent Conjugation to 2'-Amino-LNA ', Bioconjugate Chemistry, vol. 29, no. 4, pp. 1025–1029 . https://doi.org/10.1021/acs.bioconjchem.8b00101 |
| DOI: | 10.1021/acs.bioconjchem.8b00101 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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