Abstract
Oligo-[α]-thymidylates have been synthesized and covalently linked to an intercalating agent (an acridine derivative) and/or to a p-azidophenacyl group. These molecules bind to a complementary oligo-[β]-deoxynucleotide. A strong stabilization is obtained by covalent attachment of the acridine derivative at the 5′ end of the oligo-[α]-deoxynucleotide. Upon excitation of the p-azidophenacyl group with ultraviolet light, the oligo-[α]-thymidylate is crosslinked to its target sequence. These crosslinks are converted to chain breaks under alkaline conditions. This allows an unambiguous assignment of the orientation of the two oligonucleotide chains. As expected, β-β hybrids have an antiparallel orientation, whereas the two chains of α-β hybrids are parallel independently of whether an intercalating agent is covalently linked to the α-oligo-nucleotide. Oligo-[α]-thymidylates covalently linked to an acridine derivative are highly resistant to endo- and exonucleases. Therefore, they could be used as anti-messengers to block mRNA translation in vivo under conditions where oligo-[β]-deoxynucleotides are usually hydrolysed.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
