Matrix-assisted laser desorption/ionization mass spectrometry of hydrophobic peptides

Hydrophobic peptides, especially those with acid-labile protecting groups, are difficult to characterize using mass spectrometric methods. We have dev eloped a new procedure for matrix-assisted laser desorption/ionization time -of-flight (MALDI-TCF) mass spectrometric analysis of such samples. Hydroph obic peptides, which are insoluble in aqueous solutions, are dissolved in c hloroform and combined with matrixes prepared in chloroform or chloroform/m ethanol solutions. The use of a common solvent for the matrix and the analy te improves the analyte isolation step in MALDI mass spectrometry, The lack of acidic solutions previously used for electrospray ionization or MALDI m ass spectrometry of hydrophobic peptides extends this methodology to cyclic or protected hydrophobic peptides. Conventional peptide matrixes, such as 2,5-dihydroxybenzoic acid and sinapinic acid, as well as 3-indoleacrylic ac id are shown to be suitable for hydrophobic peptides. Cyclic hydrophobic pe ptides and linear hydrophobic peptides with blocked termini are detected as the cation-adducted pseudomolecular ion due to the lack of suitable sites of protonation on the analyte.