Recent technological advances in rapid heating have improved process development and synthesis optimization methods for “difficult” peptides, or peptides that exhibit secondary structure formation, have adjacent beta-branched residues or adjacent sterically-hindered residues, and/or intra/intermolecular aggregation. Electromagnetic irradiation such as microwave (MW) and infrared (IR) heating provide non-contact heating of absorbing materials more rapidly than conventional heating methods. Adjacent on the electromagnetic spectrum, IR heating has been shown to have a faster time to temperature than MW and also provides the potential for scale-up.
Using the Symphony X and Tribute UV-IR with IR heating, a number of difficult peptides have been synthesized with crude purities equivalent or showing improved results over MW platforms. In some cases, highly pure peptides (crude purity > 90%) can be produced using deprotection times of just one minute and coupling times of just two minutes.
A new heating technology, induction heating, has been introduced on the Prelude X. Induction heating allows for independent, simultaneous and rapid heating of multiple reactors with increased efficiency. A comparison of results for the synthesis of a number of difficult peptides using induction, infrared, and microwave heating methods is presented.