Osawa Takashi
Graduate School of Pharmaceutical Sciences, Osaka University.
Yakugaku Zasshi. 2024;144(10):931-936. doi: 10.1248/yakushi.24-00134.
Oligonucleotides, including DNA and RNA, can be functionalized by chemical modification based on synthetic organic chemistry. For example, ligand-oligonucleotide conjugates have a wide variety of applications. Conjugates of functional ligands and oligonucleotides have attracted attention in recent years as a drug delivery system (DDS) for improving the efficacy of oligonucleotide therapeutics. In addition, oligonucleotide conjugates with drug candidate compounds as ligands have been applied to drug screening using DNA-encoded libraries (DELs). Against this background, we have focused on the development of practical synthetic methods for ligand-oligonucleotide conjugates. Recently, we have developed a new synthetic method to construct oligonucleotides conjugated with coumarins and dipeptides, which are expected to have bioactivity, for application to DDS research of oligonucleotide therapeutics and drug discovery research using DEL. In this review, we will discuss the details, including how to construct a coumarin scaffold on oligonucleotides based on Knoevenagel condensation.
包括DNA和RNA在内的寡核苷酸可以通过基于有机合成化学的化学修饰来实现功能化。例如，配体-寡核苷酸缀合物有广泛的应用。近年来，功能性配体与寡核苷酸的缀合物作为一种用于提高寡核苷酸治疗效果的药物递送系统（DDS）受到了关注。此外，以候选药物化合物为配体的寡核苷酸缀合物已被应用于使用DNA编码文库（DEL）的药物筛选。在此背景下，我们专注于开发用于配体-寡核苷酸缀合物的实用合成方法。最近，我们开发了一种新的合成方法，用于构建与香豆素和二肽缀合的寡核苷酸，这些寡核苷酸有望具有生物活性，可应用于寡核苷酸治疗的DDS研究和使用DEL的药物发现研究。在这篇综述中，我们将讨论其细节，包括如何基于Knoevenagel缩合在寡核苷酸上构建香豆素支架。
