MALDI-ToF Mass Spectrometry for Studying Noncovalent Complexes of Biomolecules

  • Stefanie Mädler
  • Elisabetta Boeri Erba
  • Renato ZenobiEmail author
Part of the Topics in Current Chemistry book series (TOPCURRCHEM, volume 331)


Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been demonstrated to be a valuable tool to investigate noncovalent interactions of biomolecules. The direct detection of noncovalent assemblies is often more troublesome than with electrospray ionization. Using dedicated sample preparation techniques and carefully optimized instrumental parameters, a number of biomolecule assemblies were successfully analyzed. For complexes dissociating under MALDI conditions, covalent stabilization with chemical cross-linking is a suitable alternative. Indirect methods allow the detection of noncovalent assemblies by monitoring the fading of binding partners or altered H/D exchange patterns.


Chemical crosslinking First shot phenomenon Intensity fading MALDI matrix SUPREX 











2-Aminonicotinic acid


Atmospheric pressure






α-Cyano-4-hydroxycinnamic acid




Dihydroxybenzoic acid


Deoxyribonucleic acid


Electrospray ionization


Ferulic acid


Human estrogen receptor α ligand binding domain


Human immunodeficiency virus


3-Hydroxypicolinic acid




Isobaric tag for relative and absolute quantitation


Association constant


Dissociation constant


Laser induced liquid beam or bead ionization/desorption


Matrix-assisted laser desorption/ionization


Microchannel plate detector


Mass spectrometry






Ribonucleic acid


Sinapinic acid


Trifluoroacetic acid








Tryptophan repressor





We would like to thank Richard Caprioli and Dobrin Nedelkov for providing original versions of figures. Financial support for this work from the Swiss National Science Foundation (grant no. 200020_124663) is gratefully acknowledged.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Stefanie Mädler
    • 1
  • Elisabetta Boeri Erba
    • 1
  • Renato Zenobi
    • 1
    Email author
  1. 1.Department of Chemistry and Applied BiosciencesETH ZurichZurichSwitzerland

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