Loth Capucine, Charles Laurence, Lutz Jean-François, Nerantzaki Maria
Université de Strasbourg, CNRS, Institut Charles Sadron UPR22, 23 rue du Loess, 67034 Strasbourg Cedex 2, France.
Aix Marseille Université, CNRS, UMR 7273, Institute of Radical Chemistry, 13397, Marseille Cedex 20, France.
ACS Macro Lett. 2021 Apr 20;10(4):481-485. doi: 10.1021/acsmacrolett.1c00164. Epub 2021 Apr 5.
Uniform conjugates combining a DNA aptamer (either anti-MUC1 or ATP aptamer) and a synthetic polymer segment were synthesized by automated phosphoramidite chemistry. This multistep growth polymer chemistry enables the use of both natural (i.e., nucleoside phosphoramidites) and non-natural monomers (e.g., alkyl- and oligo(ethylene glycol)-phosphoramidites). Thus, in the present work, six different aptamer-polymer conjugates were synthesized and characterized by ion-exchange HPLC, circular dichroism spectroscopy, and electrospray mass spectrometry. All these methods evidenced the formation of uniform molecules with precisely controlled chain-length and monomer sequences. Furthermore, aptamer folding was not affected by polymer bioconjugation. The method described herein is straightforward and allows covalent attachment of homopolymers and copolymers to biofunctional DNA aptamers.
通过自动亚磷酰胺化学合成了结合DNA适配体（抗MUC1或ATP适配体）和合成聚合物片段的均匀共轭物。这种多步生长聚合物化学能够使用天然单体（即核苷亚磷酰胺）和非天然单体（例如烷基和聚乙二醇亚磷酰胺）。因此，在本研究中，合成了六种不同的适配体-聚合物共轭物，并通过离子交换高效液相色谱、圆二色光谱和电喷雾质谱进行了表征。所有这些方法都证明了形成了具有精确控制的链长和单体序列的均匀分子。此外，适配体折叠不受聚合物生物共轭的影响。本文所述方法简单直接，允许将均聚物和共聚物共价连接到生物功能DNA适配体上。
