Abstract
Efficient protocols based on Cu(I)-catalyzed azide–alkyne cycloaddition were developed for the synthesis of conjugates of pyrrole–imidazole polyamide minor groove binders (MGB) with fluorophores and with triplex-forming oligonucleotides (TFOs). Diverse bifunctional linkers were synthesized and used for the insertion of terminal azides or alkynes into TFOs and MGBs. The formation of stable triple helices by TFO-MGB conjugates was evaluated by gel-shift experiments. The presence of MGB in these conjugates did not affect the binding parameters (affinity and triplex stability) of the parent TFOs.
Highlights
The recognition and detection of specific sequences in native genomic double-stranded DNA is of significant importance for the development of efficient gene therapies and in vivo gene labeling [1,2,3]
Efficient protocols based on Cu(I)-catalyzed azide–alkyne cycloaddition were developed for the synthesis of conjugates of pyrrole–imidazole polyamide minor groove binders (MGB) with fluorophores and with triplex-forming oligonucleotides (TFOs)
In the first part of the present article, we describe the synthesis of various linkers bearing different functional groups for simple and accessible introduction of azide and alkyne groups into biopolymers, fluorophores and ligands
Summary
The recognition and detection of specific sequences in native genomic double-stranded DNA (dsDNA) is of significant importance for the development of efficient gene therapies and in vivo gene labeling [1,2,3]. In order to achieve a perfect fit between MGB-conjugates and dsDNA target sequences, the length and the flexibility of the linker that connects two components (polyamide and TFO or fluorophore) in the conjugates should be optimized.
Sign-in/Register to view highlights & summary 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.
