Resumé
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Organic & Biomolecular Chemistry |
| Vol/bind | 11 |
| Udgave nummer | 25 |
| Sider (fra-til) | 4240-4249 |
| ISSN | 1477-0520 |
| DOI | |
| Status | Udgivet - 2013 |
Fingeraftryk
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Peptide-LNA oligonucleotide conjugates. / Astakhova, I Kira; Hansen, Lykke Haastrup; Vester, Birte; Wengel, Jesper.
I: Organic & Biomolecular Chemistry, Bind 11, Nr. 25, 2013, s. 4240-4249.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
TY - JOUR
T1 - Peptide-LNA oligonucleotide conjugates
AU - Astakhova, I Kira
AU - Hansen, Lykke Haastrup
AU - Vester, Birte
AU - Wengel, Jesper
PY - 2013
Y1 - 2013
N2 - Although peptide-oligonucleotide conjugates (POCs) are well-known for nucleic acids delivery and therapy, reports on internal attachment of peptides to oligonucleotides are limited in number. To develop a convenient route for preparation of internally labeled POCs with improved biomedical properties, peptides were introduced into oligonucleotides via a 2'-alkyne-2'-amino-LNA scaffold. Derivatives of methionine- and leucine-enkephalins were chosen as model peptides of mixed amino acid content, which were singly and doubly incorporated into LNA/DNA strands using highly efficient copper(i)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" chemistry. DNA/RNA target binding affinity and selectivity of the resulting POCs were improved in comparison to LNA/DNA mixmers and unmodified DNA controls. This clearly demonstrates that internal attachment of peptides to oligonucleotides can significantly improve biomolecular recognition by synthetic nucleic acid analogues. Circular dichroism (CD) measurements showed no distortion of the duplex structure by the incorporated peptide chains while studies in human serum indicated superior stability of the POCs compared to LNA/DNA mixmers and unmodified DNA references. Molecular modeling suggests strong interactions between positively charged regions of the peptides and the negative oligonucleotide backbones which leads to clamping of the peptides in a fixed orientation along the duplexes.
AB - Although peptide-oligonucleotide conjugates (POCs) are well-known for nucleic acids delivery and therapy, reports on internal attachment of peptides to oligonucleotides are limited in number. To develop a convenient route for preparation of internally labeled POCs with improved biomedical properties, peptides were introduced into oligonucleotides via a 2'-alkyne-2'-amino-LNA scaffold. Derivatives of methionine- and leucine-enkephalins were chosen as model peptides of mixed amino acid content, which were singly and doubly incorporated into LNA/DNA strands using highly efficient copper(i)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" chemistry. DNA/RNA target binding affinity and selectivity of the resulting POCs were improved in comparison to LNA/DNA mixmers and unmodified DNA controls. This clearly demonstrates that internal attachment of peptides to oligonucleotides can significantly improve biomolecular recognition by synthetic nucleic acid analogues. Circular dichroism (CD) measurements showed no distortion of the duplex structure by the incorporated peptide chains while studies in human serum indicated superior stability of the POCs compared to LNA/DNA mixmers and unmodified DNA references. Molecular modeling suggests strong interactions between positively charged regions of the peptides and the negative oligonucleotide backbones which leads to clamping of the peptides in a fixed orientation along the duplexes.
U2 - 10.1039/c3ob40786a
DO - 10.1039/c3ob40786a
M3 - Journal article
VL - 11
SP - 4240
EP - 4249
JO - Organic & Biomolecular Chemistry
JF - Organic & Biomolecular Chemistry
SN - 1477-0520
IS - 25
ER -