Abstract
This article illustrates the successful and efficient solid phase assembly of hydrophobic difficult sequence peptides following both t‐Boc and Fmoc chemistry. The peptides were synthesized on an optimized 1,4‐butanediol dimethacrylate‐crosslinked polystyrene support (BDDMA‐PS). Four difficult sequence test peptides, VAVAG, VIVIG, QVGQVELG and VQAAIDYING, were synthesized in relatively good yield and purity without any aggregation problems. The peptides were assembled on chloromethylated and 4‐hydroxymethylphenoxymethyl (HMP) BDDMA‐PS resins. The peptides were fabricated using Boc amino acid 1‐hydroxybenzotriazolyl and Fmoc amino acid pentafluorophenyl active esters in coupling reactions. The peptides after synthesis were cleaved from the polymeric support by exposing the peptidyl resin to 90% trifluroacetic acid/5% thioanisole/5% EDT mixture. The HPLC and MALDI TOF MS studies of the peptides revealed the high homogeneity of the synthesized peptides. Chloromethylated resin having a functional group loading of 1.14 mmol Cl/g was used for the synthesis. The yield and homogeneity of these peptides synthesized using the new support were high when compared with the conventional DVB‐PS resin. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd.