Electrospray noncovalent complexes

Jorgensen, T. J. D., Hvelplund, P., Andersen, J. U., Roepstorff, P. Tandem mass spectrometry of specific vs. nonspecific noncovalent complexes of vancomycin antibiotics and peptide ligands. Int J Mass Spectrom 2002, 219, 659-670. Tahallah, N., Pinkse, M., Maier, C. S., Heck, A. J. The effect of the source pressure on the abundance of ions of noncovalent protein assemblies in an electrospray ionization orthogonal time-of-fiight instrument. Rapid... 

A.K. Ganguly, B.N. Pramanik, G. Chen, A. Tsarbopoulos, Detection of noncovalent complexes by electrospray ionization mass spectrometry. In B.N. Pramanik, A.K. Ganguly, M.L. Gross (Eds.) Applied Electrospray Mass Spectrometry, Marcel Dekker, Inc., New York, 2002, pp. 361 30. 

Sarni-Manchado, P. and Cheynier, V., Study of noncovalent complexation between catechin derivatives and peptide by electrospray ionization-mass spectrometry (ESI-MS). J. Mass Spectrom. 37, 609, 2002. 

Bigler, L., Baumeler, A., Werner, C., and Hesse, M. 1996. Detection of noncovalent complexes of hydroxamic-acid derivatives by means of electrospray mass spectrometry. Helv. Chim. Acta 79, 1701-1709... 

Schwartz, B. L., Light-Wahl, K. J., and Smith, R. D. (1994). Observation of noncovalent complexes in the Avidin tetramer by electrospray ionization mass spectrometry. J. Am. Soc. Mass Spectrom. 5, 201-204. 

The observation of noncovalent complexes via electrospray ionization has generated much interest. Further fundamental work is required to address the question do the gas-phase ions observed in the mass spectra reflect what is going on in solution Although we do not have a definite answer, probing the structures and properties of gas phase noncovalent complexes is an exciting and emerging area. 

Figure 14 A conceptual representation of the BAC-MS technique, (a) The mixture solution is ionized by electrospray ionization and the complex of interest is selectively accumulated in the FTICR trap, (b) The noncovalent complex is then heated to liberate the affinity ligand species, (c) The ligand ions are retained for further CAD studies to present structural information. T represents the target biomolecules, and L represents ligands that form high-binding-affinity-specific noncovalent complexes with the target molecules. Circles (solid and empty) represent ions from other molecules present in the mixture. (Reprinted from Ref. 142.)...

Jorgensen, T.J.D. Roepstorff, P Heck, A.J.R. Direct Determination of Solution Binding Constants for Noncovalent Complexes Between Bacterial Cell Wall Peptide Analogs and Vancomycin Group Antibiotics by Electrospray Ionization Mass Spectrometry, AnaZ. Chem. IQ, 4427 432 (1998). 

Ma L, Song FR, Liu ZQ, Liu SY. Smdy on noncovalent complexes of alkaloids with DNA duplex using electrospray ionization mass spectrometry. Rapid Commun Mass Spectrom 2013 27(l) 51-8. 

Bioaffinity Characterization Mass Spectrometry (BACMS) This approach also relies on the formation of noncovalent complexes between the ligands and a target but requires no isolation step prior to their mass spectrometry analysis [105]. Instead, the ligand-target complexes formed in the solution were directly introduced into an ESI-FTMS instrument. In the FTMS cell, collisional excitation first dissociates the electrosprayed complex, and the free ligands are trapped and characterized. 

Intact protein mass spectrometry allows the molecular mass determination of either proteins or complexes of proteins and covalently bound ligands/other proteins. In a first step, the sample is desalted to detach from buffer components and small ions that would interfere through noncovalent complexes in the gas phase. Next, the isolated protein is ionized, for example, by electrospray ionization (ESI). The acid in the eluent causes protonation of the protein at basic sites, particularly lysine and arginine residues, so that m/z values of multiple species with different charges can be measured in a mass spectrometer. These data are then combined during the deconvolution process to yield the mass of the protein or complex. 

Hgure 5 Negative ion electrospray ionization mass spectrum of calmodulin (SOiimoll ) in the presence of melittin (SOnmoll ) and lOOiimoll calcium acetate, pH 5.7. Ions in the range between m/z 900 and 1600 represent uncomplexed calmodulin and ions in the range between m/z 1700 and 3000 represent the noncovalent calmodulin/melittin complex. (Reprinted by permission of Elsevier from Low temperature aqueous electrospray ionization mass spectrometry of noncovalent complexes by Veenstra TD, Tomlinson AJ, Benson L, Kumar R, and Naylor S, Journal of the American Society of Mass Spectrometry 9 580-584, 1998, by the American Society for Mass Spectrometry.)... 

Srinivasan, K. Bartlett, M.G. Comparison of cyclodextrin-harhiturate noncovalent complexes using electrospray ionization mass spectrometry and capillary electrophoresis. Rapid Commun. Mass Spectrom. 2000,14, 624-632. 

Nyadong, L., Green, M.D., De Jesus, V.R., Newton, P.N., Fernandez, F.M. (2007) Reactive Desorption Electrospray Ionization Linear Ion Trap Mass Spectrometry of Latest-generation Counterfeit Antimalarials via Noncovalent Complex Formation. Anal. Chem. 79 2150-2157. 

Aphn, R.T., Robinson, C.V., Schofield, C.J., Westwood, N.J. (1994) Does the observation of noncovalent complexes between biomolecules by electrospray ionisation mass spectrometry necessarily reflect solution interactions J. Chem. Soc., Chem. Commun., 2415-2417. 

Frycdk, P, Schug, K.A. (2007) On-line dynamic titration determination of dissociation constants for noncovalent complexes using Gaussian concentration profiles by electrospray ionization mass spectrometry. Anal. Chem., 79, 5407-5413. 

GabeUca, V., Rosu, R, De Pauw, E. (2009) A simple method to determine electrospray response factors of noncovalent complexes. Anal. Chem., 81,6708-6715. 

Jorgensen, T.J.D., Roepstorff, R, Heck, A.XR. (1998) Direct determination of solution binding constants for noncovalent complexes between bacterial cell wall analogues and vancomycin group antibiotics by electrospray ionization mass spectrometry. Anal Chem., 70, 4427-4432. 

Several noncovalent complexes exist in the aqueous medium of the cell and we hitherto had no way of observing these. However electrospray ionization can get these noncovalent complexes into gaseous phase and mass spectrometry can be used to observe these complexes. This provides us insights into specific noncovalent associations in solution. Examples of complexes that have been observed using this technique include hemoglobin complex, DNA duplex, catalytic antibody-inhibitor interactions, cell surface carbohydrates and even whole viruses. 

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