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Substrate Specificity of T7 RNA Polymerase toward Hypophosphoric Analogues of ATP. | LitMetric

Substrate Specificity of T7 RNA Polymerase toward Hypophosphoric Analogues of ATP.

ACS Omega

Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland.

Published: February 2024

AI Article Synopsis

Article Abstract

Modified nucleotides are commonly used in molecular biology as substrates or inhibitors for several enzymes but also as tools for the synthesis of modified DNA and RNA fragments. Introduction of modification into RNA, such as phosphorothioate (PS), has been demonstrated to provide higher stability, more effective transport, and enhanced activity of potential therapeutic molecules. Hence, in order to achieve widespread use of RNA molecules in medicine, it is crucial to continuously refine the techniques that enable the effective introduction of modifications into RNA strands. Numerous analogues of nucleotides have been tested for their substrate activity with the T7 RNA polymerase and therefore in the context of their utility for use in transcription. In the present studies, the substrate preferences of the T7 RNA polymerase toward β,γ-hypophospho-modified ATP derivatives for the synthesis of unmodified RNA and phosphorothioate RNA (PS) are presented. The performed studies revealed the stereoselectivity of this enzyme for α-thio-β,γ-hypo-ATP derivatives, similar to that for α-thio-ATP. Additionally, it is demonstrated herein that hypodiphosphoric acid may inhibit transcription catalyzed by T7 RNA polymerase.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10905585PMC
http://dx.doi.org/10.1021/acsomega.3c08635DOI Listing

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