Interrogating Aptamer Chemical Space Through Modified Nucleotide Substitution Facilitated by Enzymatic DNA Synthesis

Germain Niogret, Alix Bouvier‐Müller, Chiara Figazzolo, Jack M. Joyce, Frédéric Bonhomme, Patrick England, Olena Mayboroda, Riccardo Pellarin, Gilles Gasser, James H. R. Tucker, Julian A. Tanner, G. Paul Savage, Marcel Hollenstein*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Downloads (Pure)

Abstract

Chemical modification of aptamers is an important step to improve their performance and stability in biological media. This can be performed either during their identification (mod-SELEX) or after the in vitro selection process (post-SELEX). In order to reduce the complexity and workload of the post-SELEX modification of aptamers, we have evaluated the possibility of improving a previously reported, chemically modified aptamer by combining enzymatic synthesis and nucleotides bearing bioisosteres of the parent cubane side-chains or substituted cubane moieties. This method lowers the synthetic burden often associated with post-SELEX approaches and allowed to identify one additional sequence that maintains binding to the PvLDH target protein, albeit with reduced specificity. In addition, while bioisosteres often improve the potency of small molecule drugs, this does not extend to chemically modified aptamers. Overall, this versatile method can be applied for the post-SELEX modification of other aptamers and functional nucleic acids.

Original languageEnglish
Article numbere202300539
Number of pages11
JournalChemBioChem
Volume25
Issue number1
Early online date13 Oct 2023
DOIs
Publication statusPublished - 2 Jan 2024

Bibliographical note

Acknowledgments:
G.N. gratefully acknowledges a fellowship from the doctoral school MTCI from Université Paris Cité. The authors gratefully acknowledge financial support from Institut Pasteur. M.H. acknowledges financial support from the ANR grant PEPR REV CNRS MOLECULARXIV. C.F. gratefully acknowledges the Pasteur-Paris University (PPU) International Ph.D. Program and the “Ecole Doctorale Frontières de l'Innovation en Recherche et Education-Programme Bettencourt” for financial support. C.F., O.M., R.P., and M.H. thank the INCEPTION program (Investissement d'Avenir grant ANR-16-CONV-0005) for funding. J.M.J. acknowledges financial support from the ARC Industrial Transformation Training Centre for Fragment-Based Design (Project ID IC180100021) and the Australian Government.”

Copyright:
© 2023 Wiley-VCH GmbH.

Keywords

  • SELEX Aptamer Technique/methods
  • Aptamers, Nucleotide/chemistry
  • DNA
  • Nucleic Acids

Fingerprint

Dive into the research topics of 'Interrogating Aptamer Chemical Space Through Modified Nucleotide Substitution Facilitated by Enzymatic DNA Synthesis'. Together they form a unique fingerprint.

Cite this