1. Enhancing Prebiotic Phosphorylation and Modulating the Regioselectivity of Nucleosides with Diamidophosphate†
- Author
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Cruz, Harold A., Jiménez, Eddy I., and Krishnamurthy, Ramanarayanan
- Abstract
Among the many prebiotic phosphorylation chemistries investigated, diamidophosphate (DAP) has shown promising potential for nucleoside phosphorylation. Herein, we show that DAP’s phosphorylation capability is enhanced significantly (up to 90%) in wet–dry cycles by a range of prebiotically plausible pHs (6–10) and temperatures (up to 80 °C) in the presence of additives such as formamide, cyanamide, urea, guanidine, 2-aminoimidazole, and hydantoin. For ribonucleosides, the main products are the 2′,3′-cyclic phosphates along with the corresponding 2′- and 3′-phosphates, while deoxyribonucleosides form 5′- and 3′-phosphates, the ratios of which are affected by cycles and the presence and nature of the additives. A simple change of temperature to 80 °C with additives leads to higher conversion yields (≈80–90%) with an increased level of 5′-phosphorylation (≈40–49%). This demonstration of enhancing and controlling the regioselectivity of DAP-mediated phosphorylation by a range of additives and conditions potentiates transitioning to the search for more efficient catalysts, enabling regiospecific phosphorylations and oligonucleotide formation in the same milieu and setting.
- Published
- 2023
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