Metalloproteins participate in many important biological processes, of which metal-binding sites are often located at the active site. In particular, a Zinc ion is essential as a structural factor of zinc finger proteins which constitute one of the most common DNA binding motif. In therapeutics, there have been extensive efforts to artificially design new types of Zinger finger proteins and also to develop a method which can facilitate the screening of the designed proteins. The main target of the screening has been their binding affinity to the targeted DNAs. Traditionally, spectroscopic tools, such as CD, NMR, and fluorescence measurements, have been successfully used. In our study, we tested the applicability of the electrospray ionization mass spectrometry as an alternative tool for the screening purpose. We also determined the Zn2+ binding affinity for a variety of artificially designed peptides. In the symposium, our recent results and its potential applications will be presented.