Modulation of the Properties of Nucleic Acids through Structural Modifications

核酸对许多基本的生物过程至关重要。它们携带遗传信息，并通过复制、转录和翻译传递信息。这些分子在许多细胞过程中也被认为具有调节作用。该建议旨在将独特的结构片段引入核酸，从而赋予这些分子特性，从而进一步了解基本的生物过程。在这方面，将研究三种化学方法。首先，一种方法代谢标记核酸将探讨。这种化学反应是基于四嗪和张力烯烃之间的反电子需求diols - alder反应。有人提出，一个紧张的烯烃部分将并入核苷，随后，并入核酸酶。结合后，将加入与BODIPY荧光团（四氮-BODIPY共轭形式的非荧光）共价连接的四氮，其中发生反向电子需求Diels-Alder反应以恢复荧光。由于这些反应通常非常快，这种化学几乎可以实时跟踪涉及核酸的细胞过程，重要的是，在最小的荧光背景下。第二,

Nucleic acids are crucial for many fundamental biological processes. They carry genetic information, and transmit it through replication, transcription and translation. These molecules are also recognized for their regulatory roles in many cellular processes. This proposal aims at approaches to introduce unique structural moieties into nucleic acids and consequently, confer properties to these molecules that will further our knowledge on the fundamental biological processes. In this regard, three chemical methods will be investigated. First, a methodology to metabolically label nucleic acids will be explored. This chemistry is based on the inverse Electron Demand Diels-Alder reaction between tetrazine and strained alkenes. It is proposed that a strained alkene moiety will be incorporated into nucleosides and subsequently, incorporated into nucleic acids enzymatically. Upon this incorporation, tetrazine that is covalently linked to a BODIPY fluorophore (non-fluorescent in the form of tetrazine-BODIPY conjugate) will be added, where an inverse Electron Demand Diels-Alder reaction takes place to restore the fluorescence. As such reactions are typically very fast, this chemistry will virtually allow for real-time tracking of cellular processes involving nucleic acids, and importantly, with minimal fluorescent background. Second,