Electrospray ionization mass spectrometry for the study of non-covalent complexes: an emerging technology

✍ Scribed by Pramanik, Birendra N.; Bartner, Peter L.; Mirza, Urooj A.; Liu, Yan-Hui; Ganguly, Ashit K.

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 546 KB
• Volume: 33
• Category: Article
• ISSN: 1076-5174
• DOI: 10.1002/(sici)1096-9888(1998100)33:10<911::aid-jms737>3.0.co;2-5

✦ Synopsis

The detection of non-covalent complexes in the mass range 19 000-34 000 Da, using electrospray ionization mass spectrometry (ESI-MS), is reviewed. The examples discussed include (1) a protein-ligand interaction (ras-GDP), (2) an inhibitor-protein-ligand interaction (SCH 54292/SCH 54341-ras-GDP), (3) a protein-protein interaction (c-IFN homodimer) and (4) a protein-metal complex [ HCV (1-181)-Zn ] . In each case, the ESI-MS method is capable of releasing the intact non-covalent complex from its native solution state into the gas phase in the form of multiply-charge ions. The molecular masses of these complexes were determined with a mass accuracy of better than 0.01% , which is far superior to the traditional methods of sodium dodecyl sulfate polyacrylamide gel electrophoresis and gel permeation chromatography. The method provides the researcher with a quick, reliable and reproducible method for probing difficult biological problems. The key to success in the study of non-covalent complexes depends on careful understanding and manipulation of ESI source parameters and sample solution conditions ; special care must be taken with the source oriüce potential and the solution pH and organic co-solvents must be avoided. This paper also illustrates the usefulness of ESI-MS for addressing biological problems leading to the discovery of new therapeutics ; the approach involves the rapid screening of potential drug candidates, such as weakly bound inhibitors.