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Updated: Jan 17, 2026

Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates
Published on: March 6, 2019
Novel Disulfide-Containing Linkages of Pyrimidine Nucleobases to Solid Supports: A Versatile Platform for
Nicholas G Horton1, Jagandeep S Saraya1, Derek K O'Flaherty1
1Department of Chemistry, University of Guelph, 50 Stone Rd E, Guelph, ON N1G 2W1, Canada.
Abstract:
Conjugation of ligands to oligonucleotides is a prominent strategy to enhance (bio)properties of nucleic acids such as cellular uptake/delivery, bioavailability, detection/tracking, and more. Here, we report a simple, cost-effective, and streamlined methodology for the incorporation of various conjugation handles into DNA and RNA. Pyrimidine nucleosides are linked to the solid support via a disulfide-containing linker covalently attached through the nucleobase, removing the typical sugar point-of-attachment requirement. We showcase a conjugation strategy in which nucleic acid strands can be permanently tagged with a ligand (via an azido group) and reversibly conjugated to another (via the linker containing a disulfide and primary amino group). Freed thiols can undergo further conjugation in certain constructs. Ultimately, our conjugation handles containing various orthogonal functional groups (e.g., azido, amino, and disulfide functional groups) will find applications in biotechnology and chemical biology.
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