Tri-Cyclic Nucleobase Analogs and Their Ribosides as Substrates of Purine-Nucleoside Phosphorylases. II Guanine and Isoguanine Derivatives
Abstract
:1. Introduction
2. Results and Discussion
2.1. Properties of 1,N2-ethenoguanine and 1,N2-ethenoguanosine
2.2. Spectral Properties of N2,3-ethenoguanine
2.3. N2,3-etheno-O6-methylguanine (3)
2.4. 1,N6-etheno-isoguanine (4)
Ribosides of 1,N6-etheno-isoguanine
3. Experimental Section
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Compound | pKa ±0.1 | Form* (pH) | UV Absorption | Fluorescence | |||
---|---|---|---|---|---|---|---|
λmax {nm} | εmax {M−1cm−1} | λmax {nm} | ϕ | τ {ns} | |||
1,N2-ethenoguanine | ~2 ~9.5 | n (6) c (1) ma (11) | 287 291 303 | 9700 ~8600 7200 | - - ~400 | - - <0.01 | - - nd ** |
N9-β-d-ribofuranosyl- | 8.8 | n (6.5) c (1) ma (11) | 284 nd 307 | 11900 nd 8400 | - - ~400 | - - <0.01 | - - nd |
N2,3-ethenoguanine | ~2.5; 8.8 | n (6.5) ma (11) c (1) | 261 266 255 | 12850 11300 11500 | 400 - - | 0.02 - - | 1.38 - - |
N2,3-etheno- O6methylguanine | ~3.5; ~9 | n (6.5) c (2) ma (12) | 272 268 280 | 9900 13300 9100 | 405 395 ~380 | 0.11 0.035 <0.01 | nd nd nd |
1,N6-etheno- isoguanine | 3.5; 8.0 | n (6.5) c (2) ma (11) | 292 296 290 | 7000 7300 6900 | 415 385 350 | 0.17 0.44 ~0.01 | 5.15; 3.4 nd nd |
N9-β-d-ribofuranosyl- | 2.4; 7.1 | n (5.5) c (1.3) ma (11) | 295 294 281 | 7200 ~7000 ~7400 | 415 380 - | 0.34 0.275 <0.01 | 6.1 4.4; 0.81 nd |
N7-β-d-ribofuranosyl- | 2.8; ~8.5 | n (6) c (2) ma (9) | 294 301 297 | 7100 ~7200 ~6500 | 360 355 365 | 0.036 ~0.4 ~0.2 | 0.8; 5.2 3.5 nd |
N6-β-d-ribofuranosyl- | ~3; ~8.5 | n (6.5) c (1.7) ma (11) | 303 298 312 | 6900 nd nd | 425 405 450 | 0.66 0.82 ~0.03 | nd nd nd |
Substrate/Enzyme | Km (µM) | Vmax (relative) * | Approximate Product Ratio: N9: N7-riboside: N6-riboside |
---|---|---|---|
1,N2-ethenoguanine /calf PNP-wt** | nd | <0.5 | predominantly N9 |
1,N2-ethenoguanine /calf PNP-mutantN243D | nd | - | - |
1,N2-ethenoguanine /E.coli PNP-wt | 48 | 18 | predominantly N9 |
1,N2-ethenoguanine /E.coli PNP-mutantD204N | nd | >15 | predominantly N9 |
N2,3-ethenoguanine /calf PNP-wt | - | <0.1 | - |
N2,3-ethenoguanine /E.coli PNP-wt | - | <0.1 | - |
N2,3-etheno-O6-methylguanine /calf PNP-wt | - | <0.1 | - |
N2,3-etheno-O6-methylguanine /E.coli PNP-wt | ~6 | ~0.3 | Nd |
1,N6-ethenoisoguanine /calf PNP-wt | ~160 | 1.6 | 1:1:10 |
1,N6-ethenoisoguanine /calf PNP- mutantN243D | nd | ~1 | predominantly N6 |
1,N6-ethenoisoguanine /E.coli PNP-wt | 98 | ~24 | 1:4:0.1 |
1,N6-ethenoisoguanine /E.coli PNP-mutantD204N | nd | >5 | 5:5:0 |
Atom | Sample/Chemical Shift (PPM) | ||
---|---|---|---|
N6-riboside | N7-riboside | N9-riboside | |
H1’ | 6.511 | 5.987 | 5.712 |
H8 | 7.822 | 8.262 | 7.753 |
H10 * | 7.775 | 7.301/7.79 | 7.212/7.520 |
H11 ** | 7.827 | ||
C1’ | 90.293 | 89.833 | 89.114 |
C5 | NA | 104.600 | NA |
C6 | 138.682 | 137.918 | 141.788 |
C8 | 137.799 | 140.026 | 135.525 |
C10 | 113.386 | 130.645/113.699 | NA/111.558 |
C11 | 116.951 |
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Stachelska-Wierzchowska, A.; Wierzchowski, J.; Górka, M.; Bzowska, A.; Wielgus-Kutrowska, B. Tri-Cyclic Nucleobase Analogs and Their Ribosides as Substrates of Purine-Nucleoside Phosphorylases. II Guanine and Isoguanine Derivatives. Molecules 2019, 24, 1493. https://doi.org/10.3390/molecules24081493
Stachelska-Wierzchowska A, Wierzchowski J, Górka M, Bzowska A, Wielgus-Kutrowska B. Tri-Cyclic Nucleobase Analogs and Their Ribosides as Substrates of Purine-Nucleoside Phosphorylases. II Guanine and Isoguanine Derivatives. Molecules. 2019; 24(8):1493. https://doi.org/10.3390/molecules24081493
Chicago/Turabian StyleStachelska-Wierzchowska, Alicja, Jacek Wierzchowski, Michał Górka, Agnieszka Bzowska, and Beata Wielgus-Kutrowska. 2019. "Tri-Cyclic Nucleobase Analogs and Their Ribosides as Substrates of Purine-Nucleoside Phosphorylases. II Guanine and Isoguanine Derivatives" Molecules 24, no. 8: 1493. https://doi.org/10.3390/molecules24081493