Synthesis of 2-Substituted Adenosine Triphosphate Derivatives and their use in Enzymatic Synthesis and Postsynthetic Labelling of RNA
Language English Country Germany Media print-electronic
Document type Journal Article
Grant support
CZ.02.01.01/00/22_008/0004575
Ministry of Education, Youth and Sports
H2020-MSCA-ITN-2019-861381
Horizon 2020
PubMed
40317833
PubMed Central
PMC12177693
DOI
10.1002/cbic.202500241
Knihovny.cz E-resources
- Keywords
- DNA polymerases, RNA polymerases, click reactions, nucleosides triphosphates, nucleotides, polyA polymerase, thiol‐ene addition,
- MeSH
- Adenosine Triphosphate * chemical synthesis chemistry analogs & derivatives metabolism MeSH
- Cycloaddition Reaction MeSH
- DNA-Directed RNA Polymerases * metabolism chemistry MeSH
- DNA-Directed DNA Polymerase * metabolism chemistry MeSH
- RNA * chemistry metabolism MeSH
- Viral Proteins metabolism MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Adenosine Triphosphate * MeSH
- bacteriophage T7 RNA polymerase MeSH Browser
- DNA-Directed RNA Polymerases * MeSH
- DNA-Directed DNA Polymerase * MeSH
- RNA * MeSH
- Viral Proteins MeSH
A series of adenosine triphosphate (ATP) derivatives bearing chloro, fluoro, amino, methyl, vinyl, and ethynyl groups at position 2 are synthesized and tested as substrates for RNA and DNA polymerases. The modified nucleotides work well in in vitro transcription with T7 RNA polymerase and primer extension (PEX) using engineered DNA polymerases (TGK, 2M) except for the bulkier 2-vinyl- and 2-ethynyl-ATP derivatives that give truncated products. However, in single nucleotide incorporation followed by PEX, they still can be used for site-specific incorporation of reactive modifications into RNA that can be further used for postsynthetic labeling through thiol-ene or Cu-catalyzed alkyne-azide cycloadditions reactions. All modified ATPs work in polyadenylation catalyzed by poly(A) polymerase to form long 3'-polyA tails containing the modifications that also can be used for labeling.
See more in PubMed
Patel R., Kaki M., Potluri V. S., Kahar P., Khanna D., Hum. Vaccines Immunother. 2022, 18, 2002083. PubMed PMC
Androsavich J. R., Nat. Rev. Drug Discovery 2024, 23, 421. PubMed
a) Pardi N., Krammer F., Nat. Rev. Drug Discovery 2024, 23, 838; PubMed
b) Shi Y., Shi M., Wang Y., You J., Signal Transducion Targeted Ther. 2024, 9, 322. PubMed PMC
a) Roundtree I. A., Evans M. E., Pan T., He C., Cell 2017, 169, 1187; PubMed PMC
b) Delaunay S., Helm M., Frye M., Nat. Rev. Genet. 2024, 25, 104. PubMed
Karikó K., Muramatsu H., Welsh F. A., Ludwig J., Kato H., Akira S., Weissman D., Mol. Ther. 2008, 16, 1833. PubMed PMC
Aboshi M., Matsuda K., Kawakami D., Kono K., Kazami Y., Sekida T., Komori M., Morey A. L., Suga S., Smith J. F., Fukuhara T., Iwatani Y., Yamamoto T., Sato N., Akahata W., iScience 2024, 27, 108964. PubMed PMC
McGee J. E., Kirsch J. R., Kenney D., Cerbo F., Chavez E. C., Shih T.‐Y., Douam F., Wong W. W., Grinstaff M. W., Nat. Biotechnol. 2024, 10.1038/s41587-024-02306-z. PubMed DOI PMC
Zhang M., Singh N., Ehmann M. E., Zheng L., Zhao H., iScience 2023, 26, 107739. PubMed PMC
Bizat P. N., Sabat N., Hollenstein M., ChemBioChem 2025, e202400987. PubMed
a) Flamme M., McKenzie L. K., Sarac I., Hollenstein M., Methods 2019, 161, 64; PubMed
b) Vaught J. D., Dewey T., Eaton B. E., J. Am. Chem. Soc. 2004, 126, 11231. PubMed
Gupta M., Levine S. R., Spitale R. C., Acc. Chem. Res. 2022, 55, 2647. PubMed
Kha T.‐K., Zhao Y., Zhu R.‐Y., Chem. Eur. J. 2025, 31, e202404244. PubMed PMC
a) Lang K., Micura R., Nat. Protoc. 2008, 3, 1457; PubMed
b) Hertler J., Slama K., Schober B., Özrendeci Z., Marchand V., Motorin Y., Helm M., Nucl. Acids Res. 2022, 50, e115. PubMed PMC
Liu Y., Holmstrom E., Zhang J., Yu P., Wang J., Dyba M. A., Chen D., Ying J., Lockett S., Nesbitt D. J., Ferré‐D’Amaré A. R., Sousa R., Stagno J. R., Wang Y.‐X., Nature 2015, 522, 368. PubMed PMC
Hartstock K., Nilges B. S., Ovcharenko A., Cornelissen N. V., Püllen N., Lawrence‐Dörner A.‐M., Leidel S. A., Rentmeister A., Angew. Chem. Int. Ed 2018, 57, 6342. PubMed
Okuda T., Lenz A.‐K., Seitz F., Vogel J., Höbartner C., Nat. Chem. 2023, 15, 1523. PubMed PMC
Domnick C., Eggert F., Wuebben C., Bornewasser L., Hagelueken G., Schiemann O., Kath‐Schorr S., Angew. Chem. Int. Ed 2020, 59, 7891. PubMed PMC
Brunderová M., Havlíček V., Matyašovský J., Pohl R., Poštová Slavětínská L., Krömer M., Hocek M., Nat. Commun. 2024, 15, 3054. PubMed PMC
a) Haslecker R., Pham V. V., Glänzer D., Kreutz C., Dayie T. K., D’Souza V. M., Nat. Commun. 2023, 14, 8422; PubMed PMC
b) Grossman B. D., Beyene B. G., Tekle B., Sakowicz W., Ji X., Camacho J. M., Vaishnav N., Ahmed A., Bhandari N., Desai K., Hardy J., Hollman N. M., Marchant J., Summers M. F., J. Mol. Biol. 2025, 169073; PubMed PMC
c) Chen D., Han Z., Liang X., Liu Y., Nat. Chem. 2025, 17, 382–392. PubMed
a) George J. T., Srivatsan S. G., Chem. Commun. 2020, 56, 12307; PubMed PMC
b) George J. T., Srivatsan S. G., Bioconjug. Chem. 2017, 28, 1529. PubMed PMC
a) Brunderová M., Krömer M., Vlková M., Hocek M., Angew. Chem. Int. Ed. 2023, 62, e202213764; PubMed PMC
b) Ivancová I., Quirante T. S., Ondruš M., Pohl R., Vlková M., Žilecká E., Bouřa E., Hocek M., Commun. Chem. 2025, 8, 1. PubMed PMC
Matyašovský J., Perlíková P., Malnuit V., Pohl R., Hocek M., Angew. Chem. Int. Ed. 2016, 55, 15856. PubMed PMC
Matyašovský J., Hocek M., Org. Biomol. Chem. 2020, 18, 255. PubMed
Krömer M., Brunderová M., Ivancová I., Poštová Slavětínská L., Hocek M., ChemPlusChem 2020, 85, 1164. PubMed
Howlader A. H., Fernandez R., Tsegay P. S., Liu Y., Wnuk S. F., Molecules 2025, 30, 1358. PubMed PMC
Matyašovský J., Pohl R., Hocek M., Chem. Eur. J. 2018, 24, 14938. PubMed PMC
Xia Z., Kondhare D., Deshmukh S., Chandankar S., Leonard P., Chem. Eur. J. 2025, 31, e202500529. PubMed
Curanovic D., Cohen M., Singh I., Slagle C. E., Leslie C. S., Jaffrey S. R., Nat. Chem. Biol. 2013, 9, 671. PubMed PMC
Mitton‐Fry R. M., Eschenbach J., Schepers H., Rasche R., Erguven M., Kümmel D., Rentmeister A., Cornelissen N. V., Chem. Sci. 2024, 15, 13068. PubMed PMC
Kovács T., Ötvös L., Tetrahedron Lett. 1988, 29, 4525.
Gupta M., Singha M., Rasale D. B., Zhou Z., Bhandari S., Beasley S., Sakr J., Parker S. M., Spitale R. C., Org. Lett. 2021, 23, 7183. PubMed
Creech C., Kanaujia M., Causey C. P., Org. Biomol. Chem. 2015, 13, 8550. PubMed
Yan F., LaMarre J. M., Röhrich R., Wiesner J., Jomaa H., Mankin A. S., Galonić Fujimori D., J. Am. Chem. Soc. 2010, 132, 3953. PubMed PMC
Cozens C., Pinheiro V. B., Vaisman A., Woodgate R., Holliger P. A., Proc. Natl. Acad. Sci. 2012, 109, 8067. PubMed PMC
Dunn M. R., Otto C., Fenton K. E., Chaput J. C., ACS Chem. Biol. 2016, 11, 1210. PubMed
Freund N., Taylor A. I., Arangundy‐Franklin S., Subramanian N., Peak‐Chew S.‐Y., Whitaker A. M., Freudenthal B. D., Abramov M., Herdewijn P., Holliger P., Nat. Chem. 2023, 15, 91. PubMed PMC
Chen T., Hongdilokkul N., Liu Z., Adhikary R., Tsuen S. S., Romesberg F. E., Nat. Chem. 2016, 8, 556. PubMed PMC
Ménová P., Cahová H., Plucnara M., Havran L., Fojta M., Hocek M., Chem. Commun. 2013, 49, 4652. PubMed
Ghosh P., Kropp H. M., Betz K., Ludmann S., Diederichs K., Marx A., Srivatsan S. G., J. Am. Chem. Soc. 2022, 144, 10556. PubMed
Ghosh P., Betz K., Gutfreund C., Pal A., Marx A., Srivatsan S. G., Angew. Chem. Int. Ed. 2025, 64, e202414319. PubMed
Hoyle C. E., Bowman C. N., Angew. Chem. Int. Ed. 2010, 49, 1540. PubMed
a) Gramlich P. M. E., Wirges C. T., Manetto A., Carell T., Angew. Chem. Int. Ed. 2008, 47, 8350; PubMed
b) Gramlich P. M. E., Wirges C. T., Manetto A., Carell T., Angew. Chem. 2008, 120, 8478. PubMed
Fantoni N. Z., El‐Sagheer A. H., Brown T., Chem. Rev. 2021, 121, 7122. PubMed
