Enhancing Prebiotic Phosphorylation and Modulating the Regioselectivity of Nucleosides with Diamidophosphate

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.

A Prebiotic Precursor to Life’s Phosphate Transfer System with an ATP Analog and Histidyl Peptide Organocatalysts

“…Individual steps of a phosphate transfer system have been demonstrated in solution such as activation and trapping of orthophosphate 14,44 and phosphorylation. 70 However, a complete system has not yet been demonstrated in solution.…”

“…A key future challenge for prebiotic chemistry is to demonstrate a phosphate transfer system (including activation of orthophosphate, trapping in a KSTA molecule, and catalyzed phosphorylation), which is fully functional in solution. Individual steps of a phosphate transfer system have been demonstrated in solution such as activation and trapping of orthophosphate , and phosphorylation . However, a complete system has not yet been demonstrated in solution.…”

Cost-effective phosphates redox-neutral transformation to bench-stable phosphorylation precursor

“…Phosphorus plays a critical role in the fundamental processes of life, being involved in almost all biological activities [1][2][3][4][5][6] . For instance, organophosphorus compounds (OPCs) are essential components in natural systems, playing key roles in cell biology, [7][8][9][10][11] biosynthesis [12][13][14] , and the formation of nucleic acid frameworks [14][15][16][17][18] . Developed synthesis of OPCs relies on a redox process via P4 (thermal process) and subsequent (oxy)chlorination to produce precursorsPCl3, PCl5, PH3 and POCl3 9,[19][20][21][22] (Fig.…”