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

Autor: Niogret G; Institut Pasteur, Université Paris Cité, CNRS UMR3523, Department of Structural Biology and Chemistry, Laboratory for Bioorganic Chemistry of Nucleic Acids, 28, rue du Docteur Roux, 75724, Paris Cedex 15, France.; Structural Bioinformatics Unit, Department of Structural Biology and Chemistry, Institut Pasteur, CNRS UMR 3528, 28, rue du Docteur Roux, 75015, Paris, France., Bouvier-Müller A; Institut Pasteur, Université Paris Cité, CNRS UMR3523, Department of Structural Biology and Chemistry, Laboratory for Bioorganic Chemistry of Nucleic Acids, 28, rue du Docteur Roux, 75724, Paris Cedex 15, France., Figazzolo C; Institut Pasteur, Université Paris Cité, CNRS UMR3523, Department of Structural Biology and Chemistry, Laboratory for Bioorganic Chemistry of Nucleic Acids, 28, rue du Docteur Roux, 75724, Paris Cedex 15, France., Joyce JM; CSIRO Manufacturing, Clayton, VIC, 3168, Australia.; School of Chemistry, University of Sydney, Sydney, NSW, 2006, Australia., Bonhomme F; Institut Pasteur, Université Paris Cité, Department of Structural Biology and Chemistry, Unité de Chimie Biologique Epigénétique UMR CNRS 3523, 28, rue du Docteur Roux, CEDEX 15, 75724, Paris, France., England P; Plateforme de Biophysique Moléculaire, C2RT, Institut Pasteur, CNRS UMR 3528, Paris, France., Mayboroda O; Institut Pasteur, Université Paris Cité, CNRS UMR3523, Department of Structural Biology and Chemistry, Laboratory for Bioorganic Chemistry of Nucleic Acids, 28, rue du Docteur Roux, 75724, Paris Cedex 15, France.; Structural Bioinformatics Unit, Department of Structural Biology and Chemistry, Institut Pasteur, CNRS UMR 3528, 28, rue du Docteur Roux, 75015, Paris, France., Pellarin R; Structural Bioinformatics Unit, Department of Structural Biology and Chemistry, Institut Pasteur, CNRS UMR 3528, 28, rue du Docteur Roux, 75015, Paris, France., Gasser G; Chimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, Laboratory for Inorganic Chemical Biology, 75005, Paris, France., Tucker JHR; School of Chemistry, University of Birmingham, Birmingham, B15 2TT, UK., Tanner JA; School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China., Savage GP; CSIRO Manufacturing, Clayton, VIC, 3168, Australia., Hollenstein M; Institut Pasteur, Université Paris Cité, CNRS UMR3523, Department of Structural Biology and Chemistry, Laboratory for Bioorganic Chemistry of Nucleic Acids, 28, rue du Docteur Roux, 75724, Paris Cedex 15, France.
Jazyk: angličtina
Zdroj: Chembiochem : a European journal of chemical biology [Chembiochem] 2024 Jan 02; Vol. 25 (1), pp. e202300539. Date of Electronic Publication: 2023 Oct 30.
DOI: 10.1002/cbic.202300539
Abstrakt: 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.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
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