Comparative evaluation of four trityl‐type amidomethyl polystyrene resins in Fmoc solid phase peptide synthesis

Abstract Four trityl‐type (i.e. non‐substituted trityl‐, o‐Cl‐trityl‐, o‐F‐trityl‐ and p‐CN‐trityl‐) amidomethyl polystyrene resins were evaluated comparatively, in terms of the stability of the trityl‐ester bond in slightly acidic dichloromethane solutions, and the p‐CN‐trityl‐amidomethyl polystyrene resin was found to be the most stable of them. The above resins were applied, in parallel with Wang benzyl‐type resin, well known for its stability in mild acidic conditions, to the Fmoc solid phase synthesis of the 43‐amino acid residue long bioactive peptide thymosin beta‐4. Independent of their differences in acid sensitivity, the resins seemed to function equally well under the conditions used, since pure thymosin beta‐4 was obtained with a final yield of approximately 30% from each resin. The trityl‐type amidomethyl polystyrene resins were also applied, in parallel with the Wang resin, to the Fmoc solid phase synthesis of a bioactive peptide containing proline at its C ‐terminus, i.e. the N ‐terminal tetrapeptide of thymosin beta‐4, AcSDKP. In this case, the best yield (87%) was obtained with the o‐Cl‐trityl‐amidomethyl polystyrene resin, which may be the resin of choice, of those studied, for the Fmoc solid phase peptide synthesis. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.