Peptide-oligonucleotide conjugates (POCs) are interesting molecules as they covalently combine 2 of the most important biomacromolecules. Sometimes, the synthesis of POCs involves unexpected difficulties; however, POCs with self-assembling propensity are even harder to synthesize and purify. Here, we show that solid-phase peptide fragment condensation combined with thiol-maleimide or copper-catalyzed azide-alkyne cycloaddition click chemistries is useful for the syntheses of self-assembling POCs. We describe guidelines for the selection of reactive functional groups and their placement during the conjugation reaction and consider the cost-effectiveness of the reaction. Purification is another important challenge during the preparation of POCs. Our results show that polyacrylamide gel electrophoresis under denaturing conditions is most suitable to recover a high yield of self-assembling POCs. This report provides the first comprehensive study of the preparation of self-assembling POCs, which will lay a foundation for the development of elegant and sophisticated molecular assemblies.
Bibliographical noteFunding Information:
Yonsei University Future‐Leading Research Initiative; Graduate school of Yonsei University research scholarship grants in 2018; Agency for Defense Development; National Research Foundation (NRF) of Korea, Grant/ Award Number: 2017R1A2A2A05069773
This work was supported by grants from the National Research Foundation (NRF) of Korea (2017R1A2A2A05069773), the Agency for Defense Development, and Yonsei University Future‐Leading Research Initiative.
This work was supported by grants from the National Research Foundation (NRF) of Korea (2017R1A2A2A05069773), the Agency for Defense Development, and Yonsei University Future-Leading Research Initiative.
Copyright © 2018 European Peptide Society and John Wiley & Sons, Ltd.
All Science Journal Classification (ASJC) codes
- Structural Biology
- Molecular Medicine
- Molecular Biology
- Drug Discovery
- Organic Chemistry