Surfactant-aided, matrix assisted laser desorption/ionization mass spectrometry of hydrophobic and hydrophilic peptides

The analysis of hydrophobic and hydrophilic peptides in an aqueous medium u sing matrix-assisted laser desorption/ionization mass spectrometry (MALDI-M S) is reported. The key development allowing for simultaneous analysis of b oth hydrophobic and hydrophilic components of the sample mixture is the use of surfactants to solubilize the hydrophobic components in the MALDI matri x solution. A wide variety of anionic, cationic, zwitterionic, and nonionic surfactants were evaluated for their ability to assist in the generation o f an abundant pseudomolecular ion from a model hydrophobic peptide ([tert-b utoxycarbonyl]Glu[gamma-O-benzyl]-Ala-Leu-Ala[O-phenacyl ester]). The resul ts indicate that the most successful surfactant among those studied for ana lyzing the model hydrophobic peptide is sodium dodecyl sulfate (SDS), SDS e xhibited no interfering surfactant background ions, little to no loss of th e acid-labile protecting groups from the model hydrophobic peptide, and an abundant pseudomolecular ion of the analyte. In addition, the use of surfac tants is shown to be compatible with hydrophilic peptides as well. Mixtures of hydrophobic and hydrophilic peptides were characterized using surfactan t-aided (SA) MALDI-MS, and his demonstrated that all components are detecta ble once the surfactant is included in the sample solution. We conclude tha t the key benefit of using SA-MALDI-MS is its ability to simultaneously ana lyze hydrophobic and hydrophilic peptides from a single sample mixture, inc luding synthetic peptides containing acid- and base-labile protecting group s.