دورية أكاديمية

Diverse Reagent Scaffolds Provide Differential Selectivity of 2′-OH Acylation in RNA

التفاصيل البيبلوغرافية
العنوان: Diverse Reagent Scaffolds Provide Differential Selectivity of 2′-OH Acylation in RNA
المؤلفون: Lu Xiao (314030), Linglan Fang (6692990), Sayantan Chatterjee (9753722), Eric T. Kool (1310808)
سنة النشر: 2022
مصطلحات موضوعية: Biochemistry, Genetics, Molecular Biology, Biotechnology, Evolutionary Biology, Cancer, Infectious Diseases, Computational Biology, Chemical Sciences not elsewhere classified, Information Systems not elsewhere classified, employed deep sequencing, systematically varied structure, altered selectivity profiles, map rna structure, widely used, unpaired nucleotides, small enough, simplest reagent, selective reactions, selective labeling, rna library, reagent scaffold, protein contacts, paired ones, leaving open, improved conjugation, generally relying, conjugating rna, chiefly restricted, cell permeable
الوصف: RNA 2′-OH acylation is widely used both for mapping structure and for conjugating RNA, generally relying on selective reactions with unpaired nucleotides over paired ones. Common reagents for this acylation have been chiefly restricted to two similar aryl scaffolds, leaving open the question of how more broadly varied reagent structure might affect selectivity. Here, we prepared a set of 10 structurally diverse acylimidazole reagents and employed deep sequencing to profile their reactivity and selectivity in an RNA library of systematically varied structure. We show that structure-directed reactivity profiles vary significantly with the reagent scaffold, and we document new acylating agents that have altered selectivity profiles, including reagents that show elevated selectivity within loops, as well as compounds with reduced off-target reactivity in loop closing base pairs. Interestingly, we also show that the simplest reagent (acetylimidazole) is cell permeable and is small enough to map RNA structure in the presence of protein contacts that block other reagents. Finally, we describe reagents that show elevated selectivity within small loops, with applications in site-selective labeling. The results provide new tools for improved conjugation and mapping of RNA.
نوع الوثيقة: article in journal/newspaper
اللغة: unknown
العلاقة: https://figshare.com/articles/journal_contribution/Diverse_Reagent_Scaffolds_Provide_Differential_Selectivity_of_2_-OH_Acylation_in_RNA/21765938Test
DOI: 10.1021/jacs.2c09040.s001
الإتاحة: https://doi.org/10.1021/jacs.2c09040.s001Test
حقوق: CC BY-NC 4.0
رقم الانضمام: edsbas.88CFFCE5
قاعدة البيانات: BASE