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Developments in electrospray ionization mass spectrometry of non-covalent DNA-ligand complexes

Journal Article


Abstract


  • Many anti-cancer drugs function by binding non-covalently to double-stranded (ds) DNA. Electrospray ionization mass

    spectrometry (ESI-MS) has emerged over the past decade as a sensitive technique for the determination of stoichiometries

    and relative binding affinities of DNA–ligand interactions. The chromosome contains nucleotide sequences, for example,

    guanosine-rich regions, that predispose them to the formation of higher order structures such as quadruplexDNA(qDNA).

    Sequences that form qDNA are found in the telomeres. The proposal that ligands that stabilize qDNA might interfere with

    the activity of telomerase in cancer cells has stimulated the search for ligands that are selective forqDNAover dsDNA. The

    insights gained from the development of ESI-MS methods for analysis of non-covalent dsDNA–ligand complexes are now

    being applied in the search for qDNA-selective ligands. ESI-MS is a useful first-pass screening technique for qDNAbinding

    ligands. This short review describes some experimental considerations for ESI-MS analysis of DNA–ligand

    complexes, briefly addresses the question of whether non-covalent DNA–ligand complexes are faithfully transferred from

    solution to the gas phase, discusses ion mobility mass spectrometry as a technique for probing this issue, and highlights

    some recent ESI-MS studies of qDNA-selective ligands

Publication Date


  • 2011

Citation


  • Beck, J. L. (2011). Developments in electrospray ionization mass spectrometry of non-covalent DNA-ligand complexes. Australian Journal of Chemistry, 64 (6), 705-717.

Scopus Eid


  • 2-s2.0-79960107320

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/3788

Number Of Pages


  • 12

Start Page


  • 705

End Page


  • 717

Volume


  • 64

Issue


  • 6

Abstract


  • Many anti-cancer drugs function by binding non-covalently to double-stranded (ds) DNA. Electrospray ionization mass

    spectrometry (ESI-MS) has emerged over the past decade as a sensitive technique for the determination of stoichiometries

    and relative binding affinities of DNA–ligand interactions. The chromosome contains nucleotide sequences, for example,

    guanosine-rich regions, that predispose them to the formation of higher order structures such as quadruplexDNA(qDNA).

    Sequences that form qDNA are found in the telomeres. The proposal that ligands that stabilize qDNA might interfere with

    the activity of telomerase in cancer cells has stimulated the search for ligands that are selective forqDNAover dsDNA. The

    insights gained from the development of ESI-MS methods for analysis of non-covalent dsDNA–ligand complexes are now

    being applied in the search for qDNA-selective ligands. ESI-MS is a useful first-pass screening technique for qDNAbinding

    ligands. This short review describes some experimental considerations for ESI-MS analysis of DNA–ligand

    complexes, briefly addresses the question of whether non-covalent DNA–ligand complexes are faithfully transferred from

    solution to the gas phase, discusses ion mobility mass spectrometry as a technique for probing this issue, and highlights

    some recent ESI-MS studies of qDNA-selective ligands

Publication Date


  • 2011

Citation


  • Beck, J. L. (2011). Developments in electrospray ionization mass spectrometry of non-covalent DNA-ligand complexes. Australian Journal of Chemistry, 64 (6), 705-717.

Scopus Eid


  • 2-s2.0-79960107320

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/3788

Number Of Pages


  • 12

Start Page


  • 705

End Page


  • 717

Volume


  • 64

Issue


  • 6