Kinetic analysis of N-alkylaryl carboxamide hexitol nucleotides as substrates for evolved polymerases

DNA directed DNA polymerase; Article; DNA modification; DNA-Directed DNA Polymerase; Kinetics; Nucleotides; Protein Engineering; Substrate Specificity; Sugar Alcohols

Abstract :

[en] Six 1,5-anhydrohexitol uridine triphosphates were synthesized with aromatic substitutions appended via a carboxamide linker to the 5-position of their bases. An improved method for obtaining such 5-substituted hexitol nucleosides and nucleotides is described. The incorporation profile of the nucleotide analogues into a DNA duplex overhang using recently evolved XNA polymerases is compared. Long, mixed HNA sequences featuring the base modifications are generated. The apparent binding affinity of four of the nucleotides to the enzyme, the rate of the chemical step and of product release, plus the specificity constant for the incorporation of these modified nucleotides into a DNA duplex overhang using the HNA polymerase T6G12 I521L are determined via pre-steady-state kinetics. HNA polymers displaying aromatic functional groups could have significant impact on the isolation of stable and high-affinity binders and catalysts, or on the design of nanomaterials. © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License

Disciplines :

Microbiology

Author, co-author :

Renders, M.; KU Leuven, Rega Institute for Medical Research, Medicinal Chemistry, Rega, Herestraat 49 box 1041, Leuven, 3000, Belgium

Dumbre, S.; KU Leuven, Rega Institute for Medical Research, Medicinal Chemistry, Rega, Herestraat 49 box 1041, Leuven, 3000, Belgium

Abramov, M.; KU Leuven, Rega Institute for Medical Research, Medicinal Chemistry, Rega, Herestraat 49 box 1041, Leuven, 3000, Belgium

Kestemont, D.; KU Leuven, Rega Institute for Medical Research, Medicinal Chemistry, Rega, Herestraat 49 box 1041, Leuven, 3000, Belgium

Margamuljana, L.; KU Leuven, Rega Institute for Medical Research, Medicinal Chemistry, Rega, Herestraat 49 box 1041, Leuven, 3000, Belgium

Largy, E.; ARNA laboratory, Université de Bordeaux, INSERM U1212, CNRS UMR5320, IECB, 2 rue Robert Escarpit, Pessac, 33600, France

Cozens, C.; Structural and Molecular Biology Department, University College London, Gower Street, London, WC1E B6T, United Kingdom, Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College, University of London, Malet Street, London, WC1E 7HX, United Kingdom, LabGenius Ltd, B201.3 Biscuit Factory, 100 Drummond Road, London, SE16 4DG, United Kingdom

Vandenameele, Julie ; Université de Liège - ULiège > Département des sciences de la vie > Enzymologie et repliement des protéines

Pinheiro, V. B.; Structural and Molecular Biology Department, University College London, Gower Street, London, WC1E B6T, United Kingdom, Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College, University of London, Malet Street, London, WC1E 7HX, United Kingdom, KU Leuven, Rega Inst. for Medical Research, Medicinal Chemistry, Rega, Herestraat 49 box 1041, Leuven, 3000, Belgium

Toye, Dominique ; Université de Liège - ULiège > Department of Chemical Engineering > Génie de la réaction et des réacteurs chimiques

Frère, Jean-Marie ; Université de Liège - ULiège > Département des sciences de la vie > Macromolécules biologiques

Herdewijn, P.; KU Leuven, Rega Institute for Medical Research, Medicinal Chemistry, Rega, Herestraat 49 box 1041, Leuven, 3000, Belgium, Université d’Evry, CNRS-UMR8030/Laboratoire iSSB, CEA, DRF, IG, Genoscope, Université Paris-Saclay, Evry, 91000, France

Language :

English

Title :

Kinetic analysis of N-alkylaryl carboxamide hexitol nucleotides as substrates for evolved polymerases

Publication date :

2019

Journal title :

Nucleic Acids Research

ISSN :

0305-1048

eISSN :

1362-4962

Publisher :

Oxford University Press

Volume :

Issue :

Pages :

2160-2168

Peer reviewed :

Peer Reviewed verified by ORBi

Name of the research project :

ERC-2012-ADG 20120216/ 3206831247114N, 16100518, DGO6, 1318159

Funders :

ERC - European Research Council

Available on ORBi :

since 02 July 2020

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Bibliography

Kang,H., Fisher,M.H., Xu,D., Miyamoto,Y.J., Marchand,A., Van Aerschot,A., Herdewijn,P. and Juliano,R.L. (2004) Inhibition of MDR1 gene expression by chimeric HNA antisense oligonucleotides. Nucleic Acids Res., 32, 4411–4419.
Le,B.T., Chen,S., Abramov,M., Herdewijn,P. and Veedu,R.N. (2016) Evaluation of anhydrohexitol nucleic acid, cyclohexenyl nucleic acid and d-altritol nucleic acid-modified 2-O-methyl RNA mixmer antisense oligonucleotides for exon skipping in vitro. Chem. Commun. (Camb.), 52, 13467–13470.
Pezo,V., Liu,F.W., Abramov,M., Froeyen,M., Herdewijn,P. and Marliere,P. (2013) Binary genetic cassettes for selecting XNA-templated DNA synthesis in vivo. Angew. Chem. Int. Ed. Engl., 52, 8139–8143.
Pezo,V., Schepers,G., Lambertucci,C., Marliere,P. and Herdewijn,P. (2014) Probing ambiguous base-pairs by genetic transformation with XNA templates. ChemBioChem., 15, 2255–2258.
Pochet,S., Kaminski,P.A., Van Aerschot,A., Herdewijn,P. and Marlière,P. (2003) Replication of hexitol oligonucleotides as a prelude to the propagation of a third type of nucleic acid in vivo. C. R. Biol., 326, 1175–1184.
Taylor,A.I., Beuron,F., Peak-Chew,S.Y., Morris,E.P., Herdewijn,P. and Holliger,P. (2016) Nanostructures from synthetic genetic polymers. ChemBioChem., 17, 1107–1110.
Pinheiro,V.B. and Holliger,P. (2014) Towards XNA nanotechnology: new materials from synthetic genetic polymers. Trends Biotechnol., 32, 321–328.
Pinheiro,V.B., Taylor,A.I., Cozens,C., Abramov,M., Renders,M., Zhang,S., Chaput,J.C., Wengel,J., Peak-Chew,S.Y., McLaughlin,S.H. et al. (2012) Synthetic genetic polymers capable of heredity and evolution. Science, 336, 341–344.
Taylor,A.I., Pinheiro,V.B., Smola,M.J., Morgunov,A.S., Peak-Chew,S., Cozens,C., Weeks,K.M., Herdewijn,P. and Holliger,P. (2015) Catalysts from synthetic genetic polymers. Nature, 518, 427–430.
Diafa,S. and Hollenstein,M. (2015) Generation of aptamers with an expanded chemical repertoire. Molecules, 20, 16643–16671.
Hollenstein,M. (2015) DNA Catalysis: The chemical repertoire of DNAzymes. Molecules, 20, 20777–20804.
Mei,H., Liao,J.Y., Jimenez,R.M., Wang,Y., Bala,S., McCloskey,C., Switzer,C. and Chaput,J.C. (2018) Synthesis and evolution of a threose nucleic acid aptamer bearing 7-Deaza-7-Substituted guanosine residues. J. Am. Chem. Soc., 140, 5706–5713.
Park,C. and Raines,R.T. (2001) Quantitative analysis of the effect of salt concentration on enzymatic catalysis. J. Am. Chem. Soc., 123, 11472–11479.
Vaught,J.D., Bock,C., Carter,J., Fitzwater,T., Otis,M., Schneider,D., Rolando,J., Waugh,S., Wilcox,S.K. and Eaton,B.E. (2010) Expanding the chemistry of DNA for in vitro selection. J. Am. Chem. Soc., 132, 4141–4151.
El Safadi,Y., Paillart,J.C., Laumond,G., Aubertin,A.M., Burger,A., Marquet,R. and Vivet-Boudou,V. (2010) 5-Modified-2-dU and 2-dC as mutagenic anti HIV-1 proliferation agents: synthesis and activity. J. Med. Chem., 53, 1534–1545.
Nomura,Y., Ueno,Y. and Matsuda,A. (1997) Site-specific introduction of functional groups into phosphodiester oligodeoxynucleotides and their thermal stability and nuclease-resistance properties. Nucleic Acid Res., 25, 2784–2791.
Bhanage,B., Tambade,P., Patil,Y. and Bhanushali,M. (2008) Pd(OAc)2-Catalyzed aminocarbonylation of Aryl iodides with aromatic or aliphatic amines in water. Synthesis, 2008, 2347–2352.
Gold,L., Ayers,D., Bertino,J., Bock,C., Bock,A., Brody,E.N., Carter,J., Dalby,A.B., Eaton,B.E., Fitzwater,T. et al. (2010) Aptamer-based multiplexed proteomic technology for biomarker discovery. PLoS One, 5, e15004.
Cox,J. and Mann,M. (2011) Quantitative, high-resolution proteomics for data-driven systems biology. Annu. Rev. Biochem., 80, 273–299.
Gelinas,A.D., Davies,D.R., Edwards,T.E., Rohloff,J.C., Carter,J.D., Zhang,C., Gupta,S., Ishikawa,Y., Hirota,M., Nakaishi,Y. et al. (2014) Crystal structure of interleukin-6 in complex with a modified nucleic acid ligand. J. Biol. Chem., 289, 8720–8734.
Davies,D.R., Gelinas,A.D., Zhang,C., Rohloff,J.C., Carter,J.D., O’Connell,D., Waugh,S.M., Wolk,S.K., Mayfield,W.S., Burgin,A.B. et al. (2012) Unique motifs and hydrophobic interactions shape the binding of modified DNA ligands to protein targets. PNAS, 109, 19971–19976.
Gupta,S., Hirota,M., Waugh,S.M., Murakami,I., Suzuki,T., Muraguchi,M., Shibamori,M., Ishikawa,Y., Jarvis,T.C., Carter,J.D. et al. (2014) Chemically modified DNA aptamers bind interleukin-6 with high affinity and inhibit signaling by blocking its interaction with interleukin-6 receptor. J. Biol. Chem., 289, 8706–8719.
Hopfield,J.J. (1974) Kinetic Proofreading: A new mechanism for reducing errors in biosynthetic processes requiring high specificity. Proc. Natl. Acad. Sci. U.S.A., 71, 4135–4139.
Hathout,Y., Brody,E., Clemens,P.R., Cripe,L., DeLisle,R.K., Furlong,P., Gordish-Dressman,H., Hache,L., Henricson,E., Hoffman,E.P. et al. (2015) Large-scale serum protein biomarker discovery in Duchenne muscular dystrophy. Proc. Natl. Acad. Sci. U.S.A., 112, 7153–7158.
Rohloff,J.C., Gelinas,A.D., Jarvis,T.C., Ochsner,U.A., Schneider,D.J., Gold,L. and Janjic,N. (2014) Nucleic acid ligands with Protein-like side Chains: Modified aptamers and their use as diagnostic and therapeutic agents. Mol. Ther. Nucleic Acids, 3, e201.
Tarasow,T.M., Tarasow,S.L. and Eaton,B.E. (1997) RNA-catalysed carbon-carbon bond formation. Nature, 389, 54–57.
Wiegand,T.W., Janssen,R.C. and Eaton,B.E. (1997) Selection of RNA amide synthases. Chem. Biol., 4, 675–683.
Chen,Y., Wiesmann,C., Fuh,G., Li,B., Christinger,H.W., McKay,P., de Vos,A.M. and Lowman,H.B. (1999) Selection and analysis of an optimized anti-VEGF antibody: crystal structure of an affinity-matured Fab in complex with antigen. J. Mol. Biol., 293, 865–881.
Fellouse,F.A., Wiesmann,C. and Sidhu,S.S. (2004) Synthetic antibodies from a four-amino-acid code: a dominant role for tyrosine in antigen recognition. Proc. Natl. Acad. Sci. U.S.A., 101, 12467–12472.
Johnson,K.A. (1992) 1 Transient-State kinetic analysis of enzyme reaction pathways. 20, 1–61.
Johnson,K.A. (1995) Rapid quench kinetic analysis of polymerases, adenosinetriphosphatases, and enzyme intermediates. Methods Enzymol., 249, 38–61.
Abramov,M. and Herdewijn,P. (2007) Synthesis of altritol nucleoside phosphoramidites for oligonucleotide synthesis. Curr. Protoc. Nucleic Acid Chem., doi:10.1002/0471142700.nc0118s30.
Ostrowski,T., Wroblowski,B., Busson,R., Rozenski,J., De Clercq,E., Bennett,M.S., Champness,J.N., Summers,W.C., Sanderson,M.R. and Herdewijn,P. (1998) 5-Substituted pyrimidines with a 1,5-anhydro-2, 3-dideoxy-D-arabino-hexitol moiety at N-1: synthesis, antiviral activity, conformational analysis, and interaction with viral thymidine kinase. J. Med. Chem., 41, 4343–4353.
Ren,W. and Yamane,M. (2010) Mo(CO)(6)-mediated carbamoylation of aryl halides. J. Org. Chem., 75, 8410–8415.
Wannberg,J. and Larhed,M. (2003) Increasing rates and scope of reactions: sluggish amines in microwave-heated aminocarbonylation reactions under air. J. Org. Chem., 68, 5750–5753.
Rösch,H., Fröllich,A., Ortigao,J.F.R., Montenarh,M. and Seliger,H. (1990) Patent US US5750669A.
Hipolito,C.J., Hollenstein,M., Lam,C.H. and Perrin,D.M. (2011) Protein-inspired modified DNAzymes: dramatic effects of shortening side-chain length of 8-imidazolyl modified deoxyadenosines in selecting RNaseA mimicking DNAzymes. Org. Biomol. Chem., 9, 2266–2273.
Perrin,D.M., Garestier,T. and Hélène,C. (1999) Expanding the catalytic repertoire of nucleic acid catalysts: simultaneous incorporation of two modified deoxyribonucleoside triphosphates bearing ammonium and imidazolyl functionalities. Nucleosides Nucleotides, 18, 377–391.
Gourlain,T., Sidorov,A., Mignet,N., Thorpe,S.J., Lee,S.E., Grasby,J.A. and Williams,D.M. (2001) Enhancing the catalytic repertoire of nucleic acids. II. Simultaneous incorporation of amino and imidazolyl functionalities by two modified triphosphates during PCR. Nucleic Acids Res., 29, 1898–1905.
Santoro,S.W., Joyce,G.F., Sakthivel,K., Gramatikova,S. and Barbas,C.F. (2000) RNA cleavage by a DNA enzyme with extended chemical functionality. J. Am. Chem. Soc., 122, 2433–2439.
Liu,C., Cozens,C., Jaziri,F., Rozenski,J., Marechal,A., Dumbre,S., Pezo,V., Marliere,P., Pinheiro,V.B., Groaz,E. et al. (2018) Phosphonomethyl oligonucleotides as Backbone-Modified artificial genetic polymers. J. Am. Chem. Soc., 140, 6690–6699.
Tsai,Y.C. and Johnson,K.A. (2006) A new paradigm for DNA polymerase specificity. Biochemistry, 45, 9675–9687.
Estep,P.A. and Johnson,K.A. (2011) Effect of the Y955C mutation on mitochondrial DNA polymerase nucleotide incorporation efficiency and fidelity. Biochemistry, 50, 6376–6386.
Gardner,A.F., Joyce,C.M. and Jack,W.E. (2004) Comparative kinetics of nucleotide analog incorporation by vent DNA polymerase. J. Biol. Chem., 279, 11834–11842.
Schermerhorn,K.M. and Gardner,A.F. (2015) Pre-steady-state kinetic analysis of a family D DNA polymerase from thermococcus sp. 9 degrees N reveals mechanisms for archaeal genomic replication and maintenance. J. Biol. Chem., 290, 21800–21810.
Rohloff,J.C., Gelinas,A.D., Jarvis,T.C., Ochsner,U.A., Schneider,D.J., Gold,L. and Janjic,N. (2014) Nucleic acid ligands with Protein-like side Chains: Modified aptamers and their use as diagnostic and therapeutic agents. Mol. Ther. Nucleic Acids, 3, e201.
Cozens,C., Pinheiro,V.B., Vaisman,A., Woodgate,R. and Holliger,P. (2012) A short adaptive path from DNA to RNA polymerases. PNAS, 109, 8067–8072.