Solid phase synthesis of bioadhesive analogue peptides with trifluoromethanesulfonic acid cleavage from PAM resin

Several decapeptides related to consensus peptide sequences found in the natural polyphenolic proteins from the sea mussels M. edulis or M. californianus have been synthesized in high yields and purities. The peptides were prepared by solid phase peptide synthesis on PAM support resins utilizing BOC protection strategies. The product peptides were then deprotected and cleaved from the PAM resins with TFMSA in a two-step procedure. The course of selective peptide deprotection with TFMSA was followed by high resolution 13C n.m.r. on aliquots of the peptide resin swollen in DMF and optimal deprotection times for batch processing of the peptide resins were chosen based on the n.m.r. results. Our two-step deprotection and cleavage procedure using TFMSA was shown to be at least as good as the usual HF procedure for the class of synthetic peptides described in this paper. N to O rearrangements of threonine and/or serine residues in the synthesized decapeptides were observed in both procedures but were reversible following treatment with ammonium bicarbonate. Coupled HPLC-u.v./vis spectroscopy, HPLC-MS and FAB MS analytical methods were used to characterize the product peptides and to provide substantial amino acid sequence information.