Vilaivan Tirayut
Organic Synthesis Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Phayathai Road, Patumwan, Bangkok 10330, Thailand.
Beilstein J Org Chem. 2018 Jan 29;14:253-281. doi: 10.3762/bjoc.14.17. eCollection 2018.
Fluorogenic oligonucleotide probes that can produce a change in fluorescence signal upon binding to specific biomolecular targets, including nucleic acids as well as non-nucleic acid targets, such as proteins and small molecules, have applications in various important areas. These include diagnostics, drug development and as tools for studying biomolecular interactions in situ and in real time. The probes usually consist of a labeled oligonucleotide strand as a recognition element together with a mechanism for signal transduction that can translate the binding event into a measurable signal. While a number of strategies have been developed for the signal transduction, relatively little attention has been paid to the recognition element. Peptide nucleic acids (PNA) are DNA mimics with several favorable properties making them a potential alternative to natural nucleic acids for the development of fluorogenic probes, including their very strong and specific recognition and excellent chemical and biological stabilities in addition to their ability to bind to structured nucleic acid targets. In addition, the uncharged backbone of PNA allows for other unique designs that cannot be performed with oligonucleotides or analogues with negatively-charged backbones. This review aims to introduce the principle, showcase state-of-the-art technologies and update recent developments in the areas of fluorogenic PNA probes during the past 20 years.
荧光寡核苷酸探针在与特定生物分子靶标结合时会产生荧光信号变化,这些靶标包括核酸以及非核酸靶标,如蛋白质和小分子,其在多个重要领域都有应用。这些领域包括诊断、药物开发以及作为原位实时研究生物分子相互作用的工具。探针通常由一条标记的寡核苷酸链作为识别元件,以及一个信号转导机制组成,该机制可将结合事件转化为可测量的信号。虽然已经开发了多种信号转导策略,但对识别元件的关注相对较少。肽核酸(PNA)是DNA模拟物,具有多种有利特性,使其成为开发荧光探针的天然核酸的潜在替代品,包括其极强且特异的识别能力、出色的化学和生物学稳定性,以及与结构化核酸靶标结合的能力。此外,PNA的不带电荷主链允许进行其他独特设计,而这些设计是带负电荷主链的寡核苷酸或类似物无法实现的。本综述旨在介绍荧光PNA探针的原理,展示其最新技术,并更新过去20年中荧光PNA探针领域的最新进展。