STUDIES ON THE SYNTHESIS OF THE TOXINS, PARDAXIN, DELTA-TOXIN AND THEIR ANALOGS BY SOLID-PHASE METHODS

Studies in our laboratory have been directed towards understanding the mechanism of action of two hydrophobic toxins, pardaxin comprising 33 residues and delta-toxin comprising 26 residues. Since isolation of t hese peptides in large amounts from natural sources is not convenient, we have explored synthetic approaches to get these peptides as well a s their analogs. We have used chemistry specific to fluorenylmethoxyca rbonyl (Fmoc) and t-butyloxycarbonyl (Boc) amino acids. Synthesis spec ific for Fmoc amino acids was carried out manually as well as on a sem i-automated continuous now peptide synthesizer. Synthesis specific for Boc amino acids was carried out manually. The protocols used by us ha ve yielded 15-33 residue peptides which are of high purity. Even in pe ptides where heterogeneity was present, pure peptide could be obtained in good yields using simple gradients in fast performance liquid chro matography. The synthesis of pardaxin, delta-toxin and several analogs should help in identifying the molecular determinants of biological a ctivity.