Reactivity profiling for high yielding Ynamine-tagged oligonucleotide click chemistry bioconjugations
Peschke, Frederik and Taladriz-Sender, Andrea and Watson, Allan J.B. and Burley, Glenn A. (2024) Reactivity profiling for high yielding Ynamine-tagged oligonucleotide click chemistry bioconjugations. Bioconjugate Chemistry. ISSN 1520-4812 (https://doi.org/10.1021/acs.bioconjchem.4c00353)
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Abstract
The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is a key ligation tool used to prepare bioconjugates. Despite the widespread utility of CuAAC to produce discrete 1,4-triazole products, the requirement of a Cu catalyst can result in oxidative damage to these products. Ynamines are superior reactive groups in CuAAC reactions and require lower Cu loadings to produce 1,4-triazole products. This study discloses a strategy to identify optimal reaction conditions for the formation of oligodeoxyribonucleotide (ODN) bioconjugates. First, the surveying of reaction conditions identified that the ratio of Cu to the choice of reductant (i.e., either sodium ascorbate or glutathione) influences the reaction kinetics and the rate of degradation of bioconjugate products. Second, optimized conditions were used to prepare a variety of ODN-tagged products and ODN-protein conjugates and compared to conventional CuAAC and Cu-free azide-alkyne (3 + 2)cycloadditions (SPAAC), with ynamine-based examples being faster in all cases. The reaction optimization platform established in this study provides the basis for its wider utility to prepare CuAAC-based bioconjugates with lower Cu loadings while maintaining fast reaction kinetics.
ORCID iDs
Peschke, Frederik, Taladriz-Sender, Andrea ORCID: https://orcid.org/0000-0002-8274-4761, Watson, Allan J.B. and Burley, Glenn A.;-
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Item type: Article ID code: 90820 Dates: DateEvent10 October 2024Published10 October 2024Published Online2 October 2024AcceptedSubjects: Medicine > Biomedical engineering. Electronics. Instrumentation
Technology > Chemical engineeringDepartment: Faculty of Science > Pure and Applied Chemistry
Technology and Innovation Centre > BionanotechnologyDepositing user: Pure Administrator Date deposited: 11 Oct 2024 10:32 Last modified: 11 Nov 2024 14:28 URI: https://strathprints.strath.ac.uk/id/eprint/90820