The synthesis of 'difficult' peptides using 2-hydroxy-4-methoxybenzyl or pseudoproline amino acid building blocks: a comparative study

A comparative study has been undertaken between Hmb-protected amino acid an d pseudoproline building block analogues for use in the solid phase synthes is of 'difficult' peptides. Both of these derivatives act by blocking inter - and intramolecular hydrogen bonding, which has been shown to be a major c ause of poor synthesis/quality/efficiency. While the two were shown to resu lt in substantial improvements in the purity of crude peptides, pseudoproli ne incorporation was found to be superior to Hmb backbone protection. This was due to slow and incomplete coupling of the amino acid immediately follo wing the Hmb amino acid. Copyright (C) 1999 European Peptide Society and Jo hn Wiley et Sons, Ltd.