N, N-dimethoxy-aminals as dynamic pH-responsive ligations for oligonucleotides
Mozaffari Majd, Mahdieh (2025-07-24)
N, N-dimethoxy-aminals as dynamic pH-responsive ligations for oligonucleotides
(24.07.2025)
Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
avoin
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2025073080256
https://urn.fi/URN:NBN:fi-fe2025073080256
Tiivistelmä
Dynamic covalent chemistry harnesses the reversible formation of chemical bonds, offering a powerful strategy for designing stimuli-responsive biomolecular systems. This thesis focuses on the development of a novel pH-sensitive linker- N, N – dimethoxy-2,2-bis (aminomethyl)propane-1,3-diol-and its application in oligonucleotide synthesis.
The linker was synthesized through a multi-step procedure and characterized using NMR and ESI-TOF HRMS. As outlined in Scheme 1, two synthetic strategies were used to incorporate it into oligonucleotide: (A) immobilization onto a solid support for terminal modification, and (B) conversion into phosphoramidite building block for intrachain modification, including hairpin-forming sequences. Both approaches produced micromole-scale modified oligonucleotide, and ESI-TOF HRMS confirmed successful incorporation.
This study introduces N, N-dimethoxy aminal as a promising base-filling linker for dynamic oligonucleotide systems and expands synthetic toolbox for constructing responsive DNA-based nanomaterials. While the pH-responsiveness of linker was not directly evaluated in this study, its chemical design enables the formation of a dynamic covalent aminal bond, which is expected to undergo reversible cleavage under mildly acidic conditions.
The linker was synthesized through a multi-step procedure and characterized using NMR and ESI-TOF HRMS. As outlined in Scheme 1, two synthetic strategies were used to incorporate it into oligonucleotide: (A) immobilization onto a solid support for terminal modification, and (B) conversion into phosphoramidite building block for intrachain modification, including hairpin-forming sequences. Both approaches produced micromole-scale modified oligonucleotide, and ESI-TOF HRMS confirmed successful incorporation.
This study introduces N, N-dimethoxy aminal as a promising base-filling linker for dynamic oligonucleotide systems and expands synthetic toolbox for constructing responsive DNA-based nanomaterials. While the pH-responsiveness of linker was not directly evaluated in this study, its chemical design enables the formation of a dynamic covalent aminal bond, which is expected to undergo reversible cleavage under mildly acidic conditions.