& To elucidate the mechanisms of the self-assembly and understand the molecular basis of the pathogenesis of conformational changes of proteins, b-amyloid or prion protein related peptides are indispensable materials. Hence, these peptides are known to have b-sheet rich structures that tend to cause difficulty in syntheses, as well as characterization by the conventional solid-phase assembly with reversed-phase columns. In general, reversed-phase HPLC combined with on-line mass spectrometry (LCMS) is routinely used for analyses and purification of resulting crude peptides and is carried out using preparative scale HPLC-columns. However, for such peptides, conventional C18 columns often give broad-peaks. We have improved separation procedures using a novel column packed with wide-pore silica having hydrophilic properties that gave separation of structural conformers with improved profiles. Thus, we have prepared several peptides for conformational studies. The same column also offers advantages for the chiral analysis of mimosine, a nonproteinogenic amino acid, which cannot be separated by the conventional C18 columns.