The enzymatic regioselective monopalmitoylation of racemic 9-(2,3-dihydroxypropyl)- adenine (DHPA), an approved antiviral agent, has been performed by an immobilized form of Candida antarctica B lipase (CAL-B) using a 4:1 DMF/hexane mixture as the reaction medium. To improve the chemical yield of the desired monopalmitoylation reaction, solid-phase chemical modifications of the lipase were evaluated. The reaction yield was successfully increased obtaining 100% product after a second treatment of the product solution with fresh immobilised chemically glycosylated-CAL-B.

Departamento de Biocatálisis Instituto de Catálisis Campus UAM Cantoblanco Madrid 28049 Spain

Institute of Organic Chemistry and Biochemistry AS CR Flemingovo nám 2 Prague 6 Czech Republic

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Kasthuri M., El Amri C., Lefort V., Perigaud C., Peyrottes S. Synthesis and study of (R)- and (S)-β-hydroxyphosphonate acyclonucleosides as structural analogues of (S)-HPMPC (cidofovir) New J. Chem. 2014;38:4736–4742. doi: 10.1039/C4NJ00813H. DOI

Głowacka I.E., Balzarini J., Andrei G., Snoeck R., Schols D., Piotrowska D.G. Design, synthesis, antiviral and cytostatic activity of ω-(1H-1,2,3-triazol-1-yl)(polyhydroxy)alkylphosphonates as acyclic nucleotide analogues. Bioorg. Med. Chem. 2014;22:3629–3641. doi: 10.1016/j.bmc.2014.05.020. PubMed DOI PMC

Kaiser M.M., Jansa P., Dračínský M., Janeba Z. A novel type of acyclic nucleoside phosphonates derived from 2-(phosphonomethoxy)propanoic acid. Tetrahedron. 2012;68:4003–4012. doi: 10.1016/j.tet.2012.03.066. PubMed DOI PMC

Xie M.-S., Niu H.-Y., Qu G.-R., Guo H.-M. The development for the synthesis of chiral acyclic nucleosides and their phosphonates Review. Tetrahedron Lett. 2014;55:7156–7166. doi: 10.1016/j.tetlet.2014.11.060. DOI

Pohl R., Postova Slavetinska L., Eng W.S., Keough D.T., Guddat L.W., Rejman D. Synthesis, conformational studies, and biological properties of phosphonomethoxyethyl derivatives of nucleobases with a locked conformation via a pyrrolidine ring. Org. Biomol. Chem. 2015;13:4693–4705. doi: 10.1039/C5OB00097A. PubMed DOI

Krečmerová M., George D., Magel S. Herpesviridae—A Look into This Unique Family of Viruses. InTech; Rijeka, Croatia: 2012. pp. 245–270.

De Clercq E., Descamps J., De Somer P., Holý A. (S)-9-(2,3-Dihydroxypropyl)adenine: An Aliphatic Nucleoside Analog with Broad-Spectrum Antiviral Activity. Science. 1978;200:563–565. doi: 10.1126/science.200.4341.563. PubMed DOI

Xie T., Lim S.M., Westover K.D., Dodge M.E., Ercan D., Ficarro S.B., Udayakumar D., Gurbani D., Tae H.S., Riddle S.M., et al. Pharmacological targeting of the pseudokinase Her3. Nat. Chem. Biol. 2014;10:1006–1012. doi: 10.1038/nchembio.1658. PubMed DOI PMC

Krečmerová M., Pohl R., Masojídková M., Balzarini J., Snoeck R., Andrei G. N4-Acyl derivatives as lipophilic prodrugs of cidofovir and its 5-azacytosine analogue,(S)-HPMP-5-azaC: Chemistry and antiviral activity. Bioorg. Med. Chem. 2014;22:2896–2906. doi: 10.1016/j.bmc.2014.03.031. PubMed DOI

Gao W.-L., Li N., Zong M.-H. Enzymatic regioselective acylation of nucleosides in biomass-derived 2-methyltetrahydrofuran: Kinetic study and enzyme substrate recognition. J. Biotechnol. 2013;164:91–96. doi: 10.1016/j.jbiotec.2013.01.004. PubMed DOI

Ravalico F., James S.L., Vyle J.S. Synthesis of nucleoside analogues in a ball mill: Fast, chemoselective and high yielding acylation without undesirable solvents. Green Chem. 2011;13:1778–1783. doi: 10.1039/c1gc15131b. DOI

Li N., Zong M.-H., Ma D. Regioselective acylation of nucleosides and their analogs catalyzed by Pseudomonas cepacia lipase: Enzyme substrate recognition. Tetrahedron. 2009;65:1063–1068. doi: 10.1016/j.tet.2008.11.045. DOI

Yuan L., Wang J., Shen W.-C. Lipidization of human interferon-alpha: A new approach toward improving the delivery of protein drugs. J. Controll. Release. 2008;129:11–17. doi: 10.1016/j.jconrel.2008.03.014. PubMed DOI

Draper J.M., Xia Z., Smith C.D. Cellular palmitoylation and trafficking of lipidated peptides. J. Lipid Res. 2007;48:1873–1884. doi: 10.1194/jlr.M700179-JLR200. PubMed DOI PMC

Reetz M.T. Biocatalysis in Organic Chemistry and Biotechnology: Past, Present, and Future. J. Am. Chem. Soc. 2013;135:12480–12496. doi: 10.1021/ja405051f. PubMed DOI

Wallace S., Balskus E.P. Opportunities for merging chemical and biological synthesis. Curr. Opin. Biotechnol. 2014;30 doi: 10.1016/j.copbio.2014.03.006. PubMed DOI PMC

Busto E., Gotor-Fernandez V., Gotor V. Hydrolases: Catalytically promiscuous enzymes for non-conventional reactions in organic synthesis. Chem. Soc. Rev. 2010;39:4504–4523. doi: 10.1039/c003811c. PubMed DOI

Mateo C., Palomo J.M., Fernandez-Lorente G., Guisan J.M., Fernandez-Lafuente R. Improvement of enzyme activity, stability and selectivity via immobilization techniques. Enzyme Microb. Technol. 2007;40:1451–1463. doi: 10.1016/j.enzmictec.2007.01.018. DOI

Adlercreutz P. Immobilisation and application of lipases in organic media. Chem. Soc. Rev. 2013;42:6406–6436. doi: 10.1039/c3cs35446f. PubMed DOI

Sheldon R.A. Enzyme Immobilization: The Quest for Optimum Performance. Adv. Synth. Catal. 2007;349:1289–1307. doi: 10.1002/adsc.200700082. DOI

Palomo J.M., Filice M. New emerging bio-catalysts design in biotransformations. Biotechnol. Adv. 2015:605–613. doi: 10.1016/j.biotechadv.2014.12.010. PubMed DOI

Romero O., Rivero C.W., Guisan J.M., Palomo J.M. Novel enzyme-polymer conjugates for biotechnological applications. Peer J. 2013;1 doi: 10.7717/peerj.27. PubMed DOI PMC

Payne R.J., Wong C.-H. Advances in chemical ligation strategies for the synthesis of glycopeptides and glycoproteins. Chem. Commun. 2010;46:21–43. doi: 10.1039/B913845E. PubMed DOI

Gutarra M.L.E., Romero O., Abian O., Torres F.A.G., Freire D.M.G., Castro A.M., Guisan J.M., Palomo J.M. Enzyme Surface Glycosylation in the Solid Phase: Improved Activity and Selectivity of Candida Antarctica Lipase B. Chem. Cat. Chem. 2011;3:1902–1910. doi: 10.1002/cctc.201100211. DOI

Díaz-Rodríguez A., Davis B.G. Chemical modification in the creation of novel biocatalysts. Opin. Chem. Biol. 2011;15:211–219. doi: 10.1016/j.cbpa.2010.12.002. PubMed DOI

Filice M., Romero O., Guisan J.M., Palomo J.M. Trans,trans-2,4-Hexadiene incorporation on enzymes for site-specific immobilization and fluorescent labeling. Org. Biomol.Chem. 2011;9:5535–5540. doi: 10.1039/c1ob05401e. PubMed DOI

Romero O., Filice M., Rivas B.D.L., Carrasco-Lopez C., Klett J., Morreale A., Hermoso J.A., Guisan J.M., Abian O., Palomo J.M. Semisynthetic peptide-lipase conjugates for improved biotransformations. Chem. Commun. 2012;48:9053–9055. doi: 10.1039/c2cc34816k. PubMed DOI

Filice M., Guisan J.M., Terreni M., Palomo J.M. Regioselective monodeprotection of peracetylated carbohydrates. Nat. Prot. 2012;7:1783–1796. doi: 10.1038/nprot.2012.098. PubMed DOI

Quintana P.G., Guillén M., Marciello M., Valero F., Palomo J.M., Baldessari A. Immobilized Heterologous Rhizopus Oryzae Lipase as an Efficient Catalyst in the Acetylation of Cortexolone. Eur. J. Org. Chem. 2012;2012:4306–4312. doi: 10.1002/ejoc.201200178. DOI

Palomo J.M., Cabrera Z. Enzymatic Desymmetrization of Prochiral Molecules. Curr. Org. Synth. 2012;9:791–805. doi: 10.2174/157017912803901628. DOI

Brabcová J., Blažek J., Janská L., Krečmerová M., Zarevúcka M. Lipases as Tools in the Synthesis of Prodrugs from Racemic 9-(2, 3-Dihydroxypropyl) adenine. Molecules. 2012;17:13813–13824. doi: 10.3390/molecules171213813. PubMed DOI PMC