| Autor: |
Wierzba AJ; Institute of Organic Chemistry, Polish Academy of Sciences, Warsaw, Poland., Wojciechowska M; Centre of New Technologies, University of Warsaw, Warsaw, Poland., Trylska J; Centre of New Technologies, University of Warsaw, Warsaw, Poland., Gryko D; Institute of Organic Chemistry, Polish Academy of Sciences, Warsaw, Poland. dorota.gryko@icho.edu.pl. |
| Jazyk: |
angličtina |
| Zdroj: |
Methods in molecular biology (Clifton, N.J.) [Methods Mol Biol] 2021; Vol. 2355, pp. 65-82. |
| DOI: |
10.1007/978-1-0716-1617-8_7 |
| Abstrakt: |
Vitamin B 12 (cobalamin, Cbl) is an essential nutrient for all mammals and some bacteria. From a chemical point of view, it is a highly functionalized molecule, which enables conjugation at multiple positions and attachment of various cargoes. Both mammalian and bacterial cells have developed a specific transport pathway for the uptake of vitamin B 12 , and as a consequence, cobalamin is an attractive candidate for the delivery of biologically relevant molecules into cells. Indeed, hybrid molecules containing vitamin B 12 in their structure have found various applications in medicinal chemistry, diagnostics, and biological sciences.Herein, we describe synthetic strategies toward the synthesis of vitamin B 12 conjugates with peptide nucleic acid (PNA ) oligomers. Such short-modified oligonucleotides targeted at bacterial DNA or RNA can act as antibacterial agents if efficiently taken up by bacterial cells. The uptake of such oligonucleotides is hindered by the bacterial cell envelope, but vitamin B 12 was found to efficiently deliver antisense PNA into Escherichia coli and Salmonella Typhimurium cells. This paves the way to the use of vitamin B 12 -PNA conjugates in antibacterial and diagnostic applications.Vitamin B 12 -PNA conjugates can be prepared via copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) that gives access to covalently linked hybrids or via connecting both building blocks by reduction-sensitive disulfide bridge. Both approaches require prior modification of vitamin B 12 by incorporation of the azide moiety or via transformation of the native functional group into a moiety reactive toward thiols. Conjugation of vitamin B 12 with PNA-tagged substrates efficiently furnishes designed conjugates.
(© 2021. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.) |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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