Academic Journal
Structure–Activity Relationships in Nonenzymatic Template‐Directed RNA Synthesis
| العنوان: | Structure–Activity Relationships in Nonenzymatic Template‐Directed RNA Synthesis |
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| المؤلفون: | Giurgiu, Constantin, Fang, Ziyuan, Aitken, Harry R. M., Kim, Seohyun Chris, Pazienza, Lydia, Mittal, Shriyaa, Szostak, Jack W. |
| المساهمون: | Howard Hughes Medical Institute |
| المصدر: | Angewandte Chemie International Edition ; volume 60, issue 42, page 22925-22932 ; ISSN 1433-7851 1521-3773 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2021 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | The template‐directed synthesis of RNA played an important role in the transition from prebiotic chemistry to the beginnings of RNA based life, but the mechanism of RNA copying chemistry is incompletely understood. We measured the kinetics of template copying with a set of primers with modified 3′‐nucleotides and determined the crystal structures of these modified nucleotides in the context of a primer/template/substrate‐analog complex. pH‐rate profiles and solvent isotope effects show that deprotonation of the primer 3′‐hydroxyl occurs prior to the rate limiting step, the attack of the alkoxide on the activated phosphate of the incoming nucleotide. The analogs with a 3 E ribose conformation show the fastest formation of 3′–5′ phosphodiester bonds. Among those derivatives, the reaction rate is strongly correlated with the electronegativity of the 2′‐substituent. We interpret our results in terms of differences in steric bulk and charge distribution in the ground vs. transition states. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1002/anie.202109714 |
| الاتاحة: | http://dx.doi.org/10.1002/anie.202109714 https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.202109714 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/anie.202109714 |
| Rights: | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| رقم الانضمام: | edsbas.841499D2 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/anie.202109714 |
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