Niogret Germain, Chériaux Camille, Bonhomme Frédéric, Levi-Acobas Fabienne, Figliola Carlotta, Ulrich Gilles, Gasser Gilles, Hollenstein Marcel
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
Chimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, Laboratory for Inorganic Chemical Biology 75005 Paris France
RSC Chem Biol. 2024 Jul 8;5(9):841-852. doi: 10.1039/d4cb00103f. eCollection 2024 Aug 28.
Photodynamic therapy (PDT) is an approved cancer treatment modality. Despite its high efficiency, PDT is limited in terms of specificity and by the poor solubility of the rather lipophilic photosensitizers (PSs). In order to alleviate these limitations, PSs can be conjugated to oligonucleotides. However, most conjugation methods often involve complex organic synthesis and result in the appendage of single modifications at the 3'/5' termini of oligonucleotides. Here, we have investigated the possibility of bioconjugating a range of known PSs by polymerase-mediated synthesis. We have prepared a range of modified nucleoside triphosphates by different conjugation methods and investigated the substrate tolerance of these nucleotides for template-dependent and -independent DNA polymerases. This method represents a mild and versatile approach for the conjugation of single or multiple PSs onto oligonucleotides and can be useful to further improve the efficiency of the PDT treatment.
光动力疗法（PDT）是一种已获批准的癌症治疗方式。尽管其效率很高，但PDT在特异性方面存在局限性，并且相当亲脂性的光敏剂（PSs）溶解性较差。为了缓解这些局限性，PSs可以与寡核苷酸结合。然而，大多数结合方法通常涉及复杂的有机合成，并且会在寡核苷酸的3'/5'末端附加单一修饰。在这里，我们研究了通过聚合酶介导的合成对一系列已知PSs进行生物结合的可能性。我们通过不同的结合方法制备了一系列修饰的核苷三磷酸，并研究了这些核苷酸对依赖模板和不依赖模板的DNA聚合酶的底物耐受性。这种方法代表了一种温和且通用的方法，可将单个或多个PSs结合到寡核苷酸上，并且可能有助于进一步提高PDT治疗的效率。
