Synthesis and Properties of α-Phosphate-Modified Nucleoside Triphosphates
Abstract
:1. Introduction
2. Chemical Synthesis of Nucleoside 5′-α-P-Modified Triphosphates
2.1. Synthesis of Nucleoside 5′-(α-P-Thio)- and 5′-(α-P-Seleno)triphosphates
2.1.1. Syntheses via a Nucleophilic Attack of Pyrophosphate on Activated Nucleoside 5′-Phosphorothioates
2.1.2. Synthesis of Nucleoside Triphosphates via a Cyclotriphosphite Intermediate (Ludwig–Eckstein Method)
2.1.3. Synthesis by the Amidophosphite Method
2.2. Synthesis of Nucleoside 5′-(α-P-Borano)triphosphates
2.2.1. Synthesis by the Amidophosphite Method
2.2.2. Synthesis through a Cyclotriphosphite Intermediate
2.3. Synthesis of Nucleoside 5′-(α-P-Alkyl)triphosphates
2.4. Synthesis of 5′-(α-P-Amido)triphosphates and 5′-(α-P-Alkylamido)triphosphates of Nucleosides
2.5. Synthesis of Nucleoside 5′-(α-P-Imido-R)triphosphates by Means of Organic Azides N3-R
2.6. Summary
3. Substrate Properties of 5′-α-P-Modified Nucleoside Triphosphates and of Oligonucleotides Synthesized from Them in Relation to Nucleic Acid-Processing Enzymes; Applications of α-Phosphate-Modified Nucleoside Triphosphates
3.1. Nucleoside 5′-(α-P-Thio)triphosphates
3.2. Nucleoside 5′-(α-P-Borano)triphosphates
3.3. Nucleoside 5′-(α-P-Alkyl)triphosphates
3.4. Nucleoside 5′-(α-P-Imido)triphosphates
4. Prospects of α-Phosphate-Modified Nucleotides for the Design of Mutant Enzymes
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Synthetic Approach | 5′-(α-P-Thio)triphosphate (Yield, %) | 5′-(α-P-Seleno)triphosphate (Yield, %) | 5′-(α-P-Borano)triphosphate (Yield, %) | 5′-(α-P-Alkyl)triphosphate (Yield, %) | 5′-(α-P-Amido)triphosphate and 5′-(α-P-Alkylamido)triphosphate (Yield, %) | 5′-(α-P-Imido)triphosphate (Yield, %) |
---|---|---|---|---|---|---|
1. Coupling of pyrophosphate with activated forms of modified NMP | dTTP (5) * [19] ATP (20) [20] ATP (25) [21] ddNTP (15–20) [23] NTP, dNTP (58–78) [25] (α-P-dithio)NTP (12–26) [26] oligonucleotides (30–50) [24] | ATP (31) [25] - | (α-P-methyl)dTTP (20–32) [36,39,40,42] (α-P-methyl)dNTP (80–85) [41] 3′-azido-5′-(α-P-methyl)dTTP (20–30) [36] (α-P-ethyl)dNTP (1–2) [43] | (α-P-amido)dTTP (72) [44] (α-P-amido)dATP (57) [44] | ||
2. Cyclic PVPVPIII-nucleoside intermediates | NTP, dNTP (60–75) [24,27] NTP, dNTP (45–60), [16] (α-P-borano, α-P-thio)dTTP (26) [30] 3′-azido-5′-(α-P-thio)dTTP (59) [31] | NTP, dNTP (30–67) [28,29] 3′-azido-5′-[α-P-seleno]dTTP (40) [31] | dNTP (25–43) [36] NTP, dNTP (35–45) [35] Acyclo-TTP (53) [34] [α-P-borano, α-P-thio]dTTP (26) [30] 5-R-dCTP (33–52) [37] ATP (31–43) [33] | (α-P-amido)dTTP [46] (α-P-alkylamido)dGTP [46] | 2′-deoxy, 5′-(α-P-(4-acetamidobenzenesulfonyl)imido)dTTP [48] | |
3. Linear PVPVPIII-nucleoside intermediates | NTP, dNTP (66–76) [10] | NTP, dNTP (54–63) [10] | NTP, dNTP (67–70) [10] | |||
4. Amidophosphite method | dTTP (30) [32] | |||||
5. Staudinger reaction | (α-P-(1,3-dimethylimidazolidin-2-ylidene)dTTP (3) [49] |
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Novgorodtseva, A.I.; Lomzov, A.A.; Vasilyeva, S.V. Synthesis and Properties of α-Phosphate-Modified Nucleoside Triphosphates. Molecules 2024, 29, 4121. https://doi.org/10.3390/molecules29174121
Novgorodtseva AI, Lomzov AA, Vasilyeva SV. Synthesis and Properties of α-Phosphate-Modified Nucleoside Triphosphates. Molecules. 2024; 29(17):4121. https://doi.org/10.3390/molecules29174121
Chicago/Turabian StyleNovgorodtseva, Alina I., Alexander A. Lomzov, and Svetlana V. Vasilyeva. 2024. "Synthesis and Properties of α-Phosphate-Modified Nucleoside Triphosphates" Molecules 29, no. 17: 4121. https://doi.org/10.3390/molecules29174121