Squaramate-linked 2'-deoxycytidine 5'-O-triphosphate was synthesized and found to be good substrate for KOD XL DNA polymerase in primer extension or PCR synthesis of modified DNA. The resulting squaramate-linked DNA reacts with primary amines to form a stable diamide linkage. This reaction was used for bioconjugations of DNA with Cy5 and Lys-containing peptides. Squaramate-linked DNA formed covalent cross-links with histone proteins. This reactive nucleotide has potential for other bioconjugations of nucleic acids with amines, peptides or proteins without need of any external reagent.

Department of Organic Chemistry Faculty of Science Charles University Prague Hlavova 8 CZ 12843 Prague 2 Czech Republic

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Flemingovo nam 2 16610 Prague 6 Czech Republic

See more in PubMed

Rohs R., Jin X., West S. M., Joshi R., Honig B., Mann R. S., Annu. Rev. Biochem. 2010, 79, 233–269. PubMed PMC

Lambert S. A., Jolma A., Campitelli L. F., Das P. K., Yin Y., Albu M., Chen X., Taipale J., Hughes T. R., Weirauch M. T., Cell 2018, 172, 650–665. PubMed

Furey T. S., Nat. Rev. Genet. 2012, 13, 840–852. PubMed PMC

Trads J. B., Tørring T., Gothelf K. V., Acc. Chem. Res. 2017, 50, 1367–1374; PubMed

Tretyakova N. Y., Groehler A., Ji S., Acc. Chem. Res. 2015, 48, 1631–1644; PubMed PMC

Niemeyer C. M., Angew. Chem. Int. Ed. 2010, 49, 1200–1216; PubMed

Angew. Chem. 2010, 122, 1220–1238;

Vinkenborg J. L., Mayer G., Famulok M., Angew. Chem. Int. Ed. 2012, 51, 9176–9180; PubMed

Angew. Chem. 2012, 124, 9311–9315;

Rosen C. B., Kodal A. L. B., Nielsen J. S., Schaffert D. H., Scavenius C., Okholm A. H., Voigt N. V., Enghild J. J., Kjems J., Tørring T., Gothelf K. V., Nat. Chem. 2014, 6, 804–809; PubMed

Nielsen T. B., Thomsen R. P., Mortensen M. R., Kjems J., Nielsen P. F., Nielsen T. E., Kodal A. L. B., Clo E., Gothelf K. V., Angew. Chem. Int. Ed. 2019, 10.1002/anie.201903134; PubMed DOI

Angew. Chem. 2019, 10.1002/ange.201903134. DOI

Norris C. L., Meisenheimer P. L., Koch T. H., J. Am. Chem. Soc. 1996, 118, 5796–5803.

Winnacker M., Breeger S., Strasser R., Carell T., ChemBioChem 2009, 10, 109–118; PubMed

Lercher L., McGouran J. F., Kessler B. M., Schofield C. J., Davis B. G., Angew. Chem. Int. Ed. 2013, 52, 10553–10558; PubMed PMC

Angew. Chem. 2013, 125, 10747–10752.

Huang H., Chopra R., Verdine G. L., Harrison S. C., Science 1998, 282, 1669–1675; PubMed

Mishina Y., He C., J. Am. Chem. Soc. 2003, 125, 8730–8731. PubMed

Dadová J., Orság P., Pohl R., Brázdová M., Fojta M., Hocek M., Angew. Chem. Int. Ed. 2013, 52, 10515–10518; PubMed

Angew. Chem. 2013, 125, 10709–10712.

Olszewska A., Pohl R., Brázdová M., Fojta M., Hocek M., Bioconjugate Chem. 2016, 27, 2089–2094. PubMed

Raiber E.-A., Portella G., Cuesta S. Martínez, Hardisty R., Murat P., Li Z., Iurlaro M., Dean W., Spindel J., Beraldi D., Liu Z., Dawson M. A., Reik, Balasubramanian W. S., Nat. Chem. 2018, 10, 1258–1266; PubMed

Balasubramanian S., Nat. Chem. 2018, 10, 1258–1266; PubMed

Li F., Zhang Y., Bai J., Greenberg M. M., Xi Z., Zhou C., J. Am. Chem. Soc. 2017, 139, 10617–10620; PubMed PMC

Ji S., Shao H., Han Q., Seiler C. L., Tretyakova N. Y., Angew. Chem. Int. Ed. 2017, 56, 14130–14134; PubMed PMC

Angew. Chem. 2017, 129, 14318–14322.

Ji S., Fu I., Naldiga S., Shao H., Basu A. K., Broyde S., Tretyakova N. Y., Nucleic Acids Res. 2018, 46, 6455–6469; PubMed PMC

Pande P., Ji S., Mukherjee S., Schärer O. D., Tretyakova N. Y., Basu A. K., Chem. Res. Toxicol. 2017, 30, 669–677; PubMed PMC

Wickramaratne S., Mukherjee S., Villalta P. W., Schärer O. D., Tretyakova N. Y., Bioconjugate Chem. 2013, 24, 1496–1506. PubMed PMC

Raindlová V., Pohl R., Hocek M., Chem. Eur. J. 2012, 18, 4080–4087; PubMed

Krömer M., Bártová K., Raindlová V., Hocek M., Chem. Eur. J. 2018, 24, 11890–11894. PubMed

Storer R. I., Aciro C., Jones L. H., Chem. Soc. Rev. 2011, 40, 2330–2346; PubMed

Wurm F. R., Klok H.-A., Chem. Soc. Rev. 2013, 42, 8220–8236; PubMed

Marchetti L. A., Kumawat L. K., Mao N., Stephens J. C., Elmes R. B. P., Chem 2019, 5, 1398–1485.

Niewiadomski S., Beebeejaun Z., Denton H., Smith T. K., Morris R. J., Wagner G. K., Org. Biomol. Chem. 2010, 8, 3488–3499; PubMed

Soukarieh F., Nowicki M. W., Bastide A., Pöyry T., Jones C., Dudek K., Patwardhan G., Meullenet F., Oldham N. J., Walkinshaw M. D., Willis A. E., Fischer P. M., Eur. J. Med. Chem. 2016, 124, 200–217; PubMed PMC

Zhang Y., Jumppanen M., Maksimainen M. M., Auno S., Awol Z., Ghemtio L., Venkannagari H., Lehtiö L., Yli-Kauhaluoma J., Xhaard H., Gennäs G. Boije Af, Bioorg. Med. Chem. 2018, 26, 1588–1597. PubMed

Sato K., Seio K., Sekine M., J. Am. Chem. Soc. 2002, 124, 12715–12724; PubMed

Dürr E.-M., Doherty W., Lee S. Y., El-Sagheer A. H., Shivalingam A., McHugh P. J., Brown T., McGouran J. F., ChemistrySelect 2018, 3, 12824–12829. PubMed PMC

Fonvielle M., Sakkas N., Iannazzo L., Le Fournis C., Patin D., Mengin-Lecreulx D., El-Sagheer A., Braud E., Cardon S., Brown T., Arthur M., Etheve-Quelquejeu M., Angew. Chem. Int. Ed. 2016, 55, 13553–13557; PubMed

Angew. Chem. 2016, 128, 13751–13755.

Hocek M., J. Org. Chem. 2014, 79, 9914–9921; PubMed

Hocek M., Acc. Chem. Res. 2019, 52, 1730–1737. PubMed

Jäger S., Rasched G., Kornreich-Leshem H., Engeser M., Thum O., Famulok M., J. Am. Chem. Soc. 2005, 127, 15071–15082. PubMed

Yoshikawa M., Kato T., Takenishi T., Tetrahedron Lett. 1967, 8, 5065–5068. PubMed

Ludwig J., Acta Biochim. Biophys. Hung. 1981, 16, 131–134. PubMed

Brazdova M., Palecek J., Cherny D. I., Billova S., Fojta M., Pecinka P., Vojtesek B., Jovin T. M., Palecek E., Nucleic Acids Res. 2002, 30, 4966–4974; PubMed PMC

Fojta M., Pivonkova H., Brazdova M., Nemcova K., Palecek J., Vojtesek B., Eur. J. Biochem. 2004, 271, 3865–3876. PubMed

Reviews:

Singh Y., Murat P., Defrancq E., Chem. Soc. Rev. 2010, 39, 2054–2070; PubMed

Merkel M., Peewasan K., Arndt S., Ploschik D., Wagenknecht H.-A., ChemBioChem 2015, 16, 1541–1553. PubMed

Enzymatic synthesis of reactive RNA probes containing squaramate-linked cytidine or adenosine for bioconjugations and cross-linking with lysine-containing peptides and proteins

Chloroacetamide-Modified Nucleotide and RNA for Bioconjugations and Cross-Linking with RNA-Binding Proteins

1,3-Diketone-Modified Nucleotides and DNA for Cross-Linking with Arginine-Containing Peptides and Proteins