Crosslinking Aptamers for Covalent Protein Targeting

01 November 2022 → 31 October 2024
Research Foundation - Flanders (FWO)
Research disciplines
  • Natural sciences
    • Bio-organic chemistry
    • Organic chemical synthesis
  • Medical and health sciences
    • Biopharmaceutics
Chemically-modified nucleosides and nucleotides DNA-protein crosslinking Aptamers
Project description

Aptamers are single-stranded nucleic acid ligands that bind targets with high affinity and specificity, owing to their characteristic three-dimensional structures. Because of these features, aptamers have been widely studied in different applications, including targeted therapy, cell staining and biosensors. Nevertheless, the translation into real-world clinical and analytical practice is still very limited, underlining the need for further research, development and optimization of aptamer-based therapeutics and diagnostics. This project aims at expanding aptamer chemistry towards aptamers able to selectively crosslink to their cell surface targets. For this purpose, furan-modified nucleosides will be incorporated in aptamer sequences, using synthetic and enzymatic approaches to construct aptamers of moderate and high complexity, respectively. The furan technology developed by the OBCR group allows spatiotemporal control of the crosslinking reaction, as only activated furan is able to form covalent bonds with the target. Selective activation is achieved by singlet oxygen, generated by light irradiation of a photosensitizer, or reactive oxygen species, endogenously produced by cells at the cell surface. The specificity of aptamer binding will be combined with the selectivity of the furan technology to investigate the potential of next generation, high affinity covalent ligands for cell-surface protein targeting.