Tetramolecular G-quadruplex formation pathways studied by electrospray mass spectrometry

[en] Electrospray mass spectrometry was used to investigate the mechanism of tetramolecular G-quadruplex formation by the DNA oligonucleotide dTG5T, in ammonium acetate. The intermediates and products were separated according to their mass (number of strands and inner cations) and quantified. The study of the temporal evolution of each species allows us to propose the following formation mechanism. (i) Monomers, dimers and trimers are present at equilibrium already in the absence of ammonium acetate. (ii) The addition of cations promotes the formation of tetramers and pentamers that incorporate ammonium ions and therefore presumably have stacked guanine quartets in their structure. (iii) The pentamers eventually disappear and tetramers become predominant. However, these tetramers do not have their four strands perfectly aligned to give five G-quartets: the structures contain one ammonium ion too few, and ion mobility spectrometry shows that their conformation is more extended. (iv) At 4°C, the rearrangement of the kinetically trapped tetramers with presumably slipped strand(s) into the perfect G-quadruplex structure is extremely slow (not complete after 4 months). We also show that the addition of methanol to the monomer solution significantly accelerates the cation-induced G-quadruplex assembly.

Research Center/Unit :

Giga-Systems Biology and Chemical Biology - ULiège

Disciplines :

Biochemistry, biophysics & molecular biology
Chemistry

Author, co-author :

Rosu, Frédéric ; Université de Liège - ULiège > Département de chimie (sciences) > GIGA-R : Laboratoire de spectrométrie de masse (L.S.M.)

Gabelica, Valérie ; Université de Liège - ULiège > Département de chimie (sciences) > GIGA-R : Laboratoire de spectrométrie de masse (L.S.M.)

Poncelet, Harmonie; Université de Liège - ULiège > Département de chimie (sciences) > GIGA-R : Laboratoire de spectrométrie de masse (L.S.M.)

De Pauw, Edwin ; Université de Liège - ULiège > Département de chimie (sciences) > GIGA-R : Laboratoire de spectrométrie de masse (L.S.M.)

Language :

English

Title :

Tetramolecular G-quadruplex formation pathways studied by electrospray mass spectrometry

Publication date :

16 April 2010

Journal title :

Nucleic Acids Research

ISSN :

0305-1048

eISSN :

1362-4962

Publisher :

Oxford University Press, Oxford, United Kingdom

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

F.R.S.-FNRS - Fonds de la Recherche Scientifique

Available on ORBi :

since 04 May 2010

Statistics

Number of views

196 (19 by ULiège)

Number of downloads

160 (2 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

103

Bibliography

Davis, J.T. and Spada,G.P. (2007) Supramolecular architectures generated by self-assembly of guanosine derivatives. Chem. Soc. Rev., 36, 296-313.
Davis,J.T. (2004) G-quartets 40 years later: from 5'-GMP to molecular biology and supramolecular chemistry. Angew. Chem. Int. Ed., 43, 668-698.
Neidle,S. (2009) The structures of quadruplex nucleic acids and their drug complexes. Curr. Opin. Struct. Biol., 19, 239-250.
Phan,A.-T., Kuryavyi,V. and Patel,D.J. (2006) DNA architecture: From G to Z. Curr. Opin. Struct. Biol., 16, 288-298.
Patel,D.J., Phan,A.T. and Kuryavyi,V. (2007) Human telomere, oncogenic promoter and 5'-UTR G-quadruplexes: Diverse higher order DNA and RNA targets for cancer therapeutics. Nucleic Acids Res., 35, 7429-7455.
Qin,Y. and Hurley,L.H. (2008) Structures, folding patterns, and functions of intramolecular DNA G-quadruplexes found in eukaryotic promoter regions. Biochimie, 90, 1149-1171.
Mergny,J.-L., Gros,J., De Cian,A., Bourdoncle,A., Rosu,F., Sacca,B., Guittat,L., Amrane,S., Mills,M., Alberti,P. et al. (2006) Energetics, kinetics and dynamics of quadruplex folding. In Neidle,S. and Balasubramanian,S. (eds), Quadruplex Nucleic Acids. The Royal Society of Chemistry, Cambridge, pp. 31-80.
Lane,A.N., Chaires,J.B., Gray,R.D. and Trent,J.O. (2008) Stability and kinetics of G-quadruplex structures. Nucleic Acids Res., 36, 5482-5515.
Alberti,P., Bourdoncle,A., Sacca,B., Lacroix,L. and Mergny,J.L. (2006) DNA nanomachines and nanostructures involving quadruplexes. Org. Biomol. Chem., 4, 3383-3391.
Aldaye,F.A., Palmer,A.L. and Sleiman,H.F. (2008) Assembling materials with DNA as the guide. Science, 321, 1795-1799.
Lena,S., Masiero,S., Pieraccini,S. and Spada,G.P. (2009) Guanosine hydrogen-bonded scaffolds: A new way to control the bottom-up realisation of well-defined nanoarchitectures. Chem. Eur. J., 15, 7792-7806.
Cohen,H., Sapir,T., Borovok,N., Molotsky,T., DiFelice,R., Kotlyar,A.B. and Porath,D. (2007) Polarizability of G4-DNA observed by electrostatic force microscopy measurements. Nano Lett., 7, 981-986.
Miannay,F.A., Banyasz,A., Gustavsson,T. and Markovitsi,D. (2009) Excited states and energy transfer in G-quadruplexes. J. Phys. Chem. C, 113, 11760-11765.
Bates,P.J., Laber,D.A., Miller,D.M., Thomas,S.D. and Trent,J.O. (2009) Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer. Exp. Mol. Pathol., 86, 151-164.
Chou,S.H., Chin,K.H. and Wang,A.H.J. (2005) DNA aptamers as potential anti-HIV agents. Trends Biochem. Sci., 30, 231-234.
Phan,A.T., Kuryavyi,V., Ma,J.B., Faure,A., Andreola,M.L. and Patel,D.J. (2005) An interlocked dimeric parallel-stranded DNA quadruplex: a potent inhibitor of HIV-1 integrase. Proc. Natl Acad. Sci. USA, 102, 634-639.
Wyatt,J.R., Davis,P.W. and Freier,S.M. (1996) Kinetics of G-quartet-mediated tetramer formation. Biochemistry, 35, 8002-8008.
D'Onofrio,J., Petraccone,L., Martino,L., Di,F.G., Iadonisi,A., Balzarini,J., Giancola,C. and Montesarchio,D. (2008) Synthesis, biophysical characterization, and anti-HIV activity of glyco-conjugated G-quadruplex-forming oligonucleotides. Bioconjug. Chem., 19, 607-616.
Bates,P.J., Laber,D.A., Miller,D.M., Thomas,S.D. and Trent,J.O. (2009) Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer. Exp. Mol. Pathol., 86, 151-164.
D'Onofrio,J., Petraccone,L., Martino,L., Di,F.G., Iadonisi,A., Balzarini,J., Giancola,C. and Montesarchio,D. (2008) Synthesis, biophysical characterization, and anti-HIV activity of glyco-conjugated G-quadruplex-forming oligonucleotides. Bioconjug. Chem., 19, 607-616.
Gu,J. and Leszczynski,J. (2002) Origin of Na+/K+ selectivity of the guanine tetraplexes in water: the theoretical rationale. J. Phys. Chem. A, 106, 529-532.
Hud,N.V., Schultze,P., Sklenar,V. and Feigon,J. (1999) Binding sites and dynamics of ammonium ions in a telomere repeat DNA quadruplex. J. Mol. Biol., 285, 233-243.
Sket,P., Crnugelj,M. and Plavec,J. (2005) Identification of mixed di-cation forms of G-quadruplex in solution. Nucleic Acids Res., 33, 3691-3697.
Mergny,J.-L., De Cian,A., Gheleb,A., Sacca,B. and Lacroix,L. (2005) Kinetics of tetramolecular quadruplexes. Nucleic Acids Res., 33, 81-94.
Bardin,C. and Leroy,J.L. (2008) The formation pathway of tetramolecular G-quadruplexes. Nucleic Acids Res., 36, 477-488.
Stefl,R., Cheatham,T.E., Spackova,N., Fadrna,E., Berger,I., Koca,J. and Sponer,J. (2003) Formation pathways of a guanine-quadruplex DNA revealed by molecular dynamics and thermodynamic analysis of the substates. Biophys. J., 85, 1787-1804.
Hofstadler,S.A. and Griffey,R.H. (2001) Analysis of noncovalent complexes of DNA and RNA by mass spectrometry. Chem. Rev., 101, 377-390.
Beck,J., Colgrave,M.L., Ralph,S.F. and Sheil,M.M. (2001) Electrospray ionization mass spectrometry of oligonucleotide complexes with drugs, metals, and proteins. Mass Spectrom. Rev., 20, 61-87.
Rosu,F., De Pauw,E. and Gabelica,V. (2008) Electrospray mass spectrometry to study drug-nucleic acid interactions. Biochimie, 90, 1074-1087.
Rosu,F., Gabelica,V., Houssier,C., Colson,P. and De Pauw,E. (2002) Triplex and quadruplex DNA structures studied by electrospray mass spectrometry. Rapid Commun. Mass Spectrom., 16, 1729-1736.
Li,H.H., Yuan,G. and Du,D.M. (2008) Investigation of formation, recognition, stabilization, and conversion of dimeric G-quadruplexes of HIV-1 integrase inhibitors by electrospray ionization mass spectrometry. J. Am. Soc. Mass Spectrom., 19, 550-559.
Smargiasso,N., Rosu,F., Hsia,W., Colson,P., Baker,E.S., Bowers,M.T., De Pauw,E. and Gabelica,V. (2008) G-quadruplex DNA assemblies: loop length, cation identity, and multimer formation. J. Am. Chem. Soc., 130, 10208-10216.
Gros,J., Rosu,F., Amrane,S., De Cian,A., Gabelica,V., Lacroix,L. and Mergny,J.L. (2007) Guanines are a quartet's best friend: Impact of base substitutions on the kinetics and stability of tetramolecular quadruplexes. Nucleic Acids Res., 35, 3064-3075.
Gabelica,V., Rosu,F. and De Pauw,E. (2009) A simple method to determine electrospray response factors of noncovalent complexes. Anal. Chem., 81, 6708-6715.
Giles,K., Pringle,S.D., Worthington,K.R., Little,D., Wildgoose,J.L. and Bateman,R.H. (2004) Applications of a travelling wave-based radio-frequencyonly stacked ring ion guide. Rapid Commun. Mass Spectrom., 18, 2401-2414.
Prislan,I., Lah,J. and Vesnaver,G. (2008) Diverse polymorphism of G-quadruplexes as a kinetic phenomenon. J. Am. Chem. Soc., 130, 14161-14169.
Hardin,C.C., Corregan,M.J., Lieberman,D.V. and Brown,B.A. II (1997) Allosteric interactions between DNA strands and monovalent cations in DNA quadruplex assembly: Thermodynamic evidence for three linked association pathways. Biochemistry, 36, 15428-15450.
Hardin,C.C., Perry,A.G. and White,K. (2000) Thermodynamic and kinetic characterization of the dissociation and assembly of quadruplex nucleic acids. Biopolymers, 56, 147-194.