Synthesis and stability studies of bicyclo[6.1.0]nonyne scaffolds for automated solid-phase oligonucleotide synthesis

Kristina Karalė; Martin Bollmark; Antanas Karalius; Mónica Lopes; Oswaldo Pérez; Roger Strömberg; Ulf Tedebark

doi:10.1039/d3ra08732h

Synthesis and stability studies of bicyclo[6.1.0]nonyne scaffolds for automated solid-phase oligonucleotide synthesis

RSC Adv. 2024 May 29;14(25):17406-17412. doi: 10.1039/d3ra08732h. eCollection 2024 May 28.

Authors

Kristina Karalė^{1

2}, Martin Bollmark², Antanas Karalius², Mónica Lopes^{2

3}, Oswaldo Pérez^{2

4}, Roger Strömberg^{1

5}, Ulf Tedebark²

Affiliations

¹ Department of Biosciences and Nutrition, Karolinska Institutet Neo 141 57 Huddinge Sweden kristina.karale@ri.se.
² RISE, Department Chemical Process and Pharmaceutical Development Forskargatan 18 SE-15136 Södertälje Sweden ulf.tedebark@ri.se.
³ School of Chemistry, University of Southampton Southampton UK.
⁴ Faculty of Pharmaceutical Sciences, University of Iceland Sæmundargata 2 102 Reykjavík Iceland.
⁵ Department of Laboratory Medicine, Karolinska Institutet ANA Futura 141 52 Huddinge Sweden.

Abstract

Two novel bicyclo[6.1.0]nonyne (BCN) linker derivatives, which can be directly incorporated into oligonucleotide sequences during standard automated solid-phase synthesis, are reported. Stabilities of BCN-carbinol and two BCN-oligonucleotides are evaluated under acidic conditions. In addition, derivatized BCN linkers (non-acidic and acid treated) are evaluated for strain-promoted alkyne-azide cycloaddition (SPAAC).