JAMES P. CAIN*, MICHAEL A. ONAIYEKAN, CHRISTINA A. CHANTELL*, CHRIS DONAT, ROBERT W. HENSLEY, MAHENDRA MENAKURU
*Corresponding authors
Protein Technologies, Inc. 4675 S. Coach Dr. Tucson, AZ 85714, USA

Abstract

A variety of peptide sequences were synthesized using a highly efficient non-microwave heating method on an automated peptide synthesizer and compared to microwave data. This particular system represents an advance over existing microwave systems in that more than one peptide can be synthesized simultaneously with heat.

INTRODUCTION

Long and difficult peptides remain a challenge in solid-phase peptide synthesis (SPPS). Sterically hindered side chains and inter- and intramolecular chain aggregation due to hydrophobic side groups can obscure the reactive site of a growing peptide chain. Several methods which have been shown to overcome these difficulties include the use of pseudoproline dipeptides (1-3), more efficient activators such as HATU or HCTU (4, 5), the choice of solvent (4) and low-loaded resins (6, 7). In each case, the synthetic challenge has been overcome by the use of one or more of these tools. Another tool which has been used in such cases is heat. In recent years, microwave heating has gained in popularity due to its ability to heat in a highly efficient way. The disadvantages to using microwave methods are they cannot be scaled up due to the inability of microwaves to penetrate a solution more than a few centimetres, and they can only be performed in one reaction vessel at a time, so they cannot be used in high-throughput applications. Luckily, recent studies comparing conventional and microwave methods concluded that the outcomes were due to the heat al ...