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Synthesis of a Thiol Building Block for the Crystallization of a Semiconducting Gyroidal Metal-sulfur Framework
Published on: April 9, 2018
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Derivatization of Solid Supports Using a Carbamate-Linked Tether Containing a Disulfide Functional Group
Jagandeep S Saraya1, Derek K O'Flaherty1
1Department of Chemistry, University of Guelph, Guelph, Canada.
Current Protocols
|August 7, 2025
Summary
This study introduces a novel disulfide linker for efficient on-column synthesis of modified oligonucleotides, including amino and phosphate modifications. This method simplifies DNA and RNA synthesis and enables the creation of amino acid-oligonucleotide conjugates.
Area of Science:
- Chemical Biology
- Oligonucleotide Synthesis
- Bioconjugation
Background:
- Chemical modifications enhance oligonucleotide functionality for applications like bioconjugation and immobilization.
- Amino modifiers are crucial for versatile post-synthetic modifications and studying early life genome replication.
- Existing methods for synthesizing modified oligonucleotides can be complex and may involve precipitation steps.
Purpose of the Study:
- To develop an economical disulfide-containing solid-support linker for on-column synthesis of modified oligonucleotides.
- To enable the synthesis of DNA and RNA with 3'-amino or 3'-phosphate modifications from unprotected mononucleosides.
- To facilitate the preparation of amino acid-oligonucleotide conjugates with improved efficiency.
Main Methods:
- On-column synthesis utilizing an orthogonal protecting group strategy with a disulfide-containing solid-support linker.
- Synthesis of DNA and RNA bearing 3'-amino-2',3'-dideoxyribosides and 2'-amino-2'-deoxynucleosides.
- Improved on-column deprotection procedure for DNA and RNA, eliminating precipitation.
- Preparation and characterization of amino acid-oligonucleotide conjugates using standard purification (SAX-HPLC) and MS.
Main Results:
- Successful on-column synthesis of DNA and RNA with 3'-amino and 3'-phosphate modifications using the disulfide linker.
- Facilitated synthesis of 3'-amino-2',3'-dideoxyribosides and 2'-amino-2'-deoxynucleosides.
- Enhanced strand recovery for certain sequences due to the elimination of the precipitation step in RNA workflows.
- Demonstrated application in synthesizing amino acid-oligonucleotide conjugates, with product identity dependent on deprotection conditions.
Conclusions:
- The disulfide-containing solid-support linker provides an efficient and economical method for on-column synthesis of modified oligonucleotides.
- The protocol simplifies DNA and RNA synthesis, offering versatility in introducing amino and phosphate modifications.
- This approach advances the preparation of complex oligonucleotide derivatives and conjugates for various biological applications.
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