For the past decade our customers have been using Biotage's microwave synthesis systems for solid phase synthesis of peptides, peptoids and peptidomimetics. In celebration of this decade of excellence, we sat down together with one of the microwave pioneers, Professor Adolf Gogoll at Uppsala University, for a chat on microwaves, peptide chemistry and exploding glass vials.
In 2002, Adolf Gogoll and Máté Erdélyi published one of the first scientific papers describing the use of precise microwave irradiation in solid phase peptide synthesis. Ten years later, their paper is still heavily cited as one of the originators of this technique.
“We knew we were early with this, but since publication we haven’t really focused on improving peptide synthesis. My interest as a scientist is not in method development. I just need methods that work” says Adolf Gogoll, Professor of Organic Chemistry at Uppsala University, Sweden.
- Why did you try microwaves for peptide synthesis?
“We thought we could really save time using microwaves, especially when creating peptides with artificial amino acids such as aniline derivatives, which are much less reactive. We first published a microwave accelerated version of the Sonogashira reaction in 2001. This reaction can take three days to complete at room temperature, but with microwaves we got it down to fifteen minutes. A recent review in Chemical Society Reviews cites us as the ones demonstrating that microwave accelerated peptide synthesis actually works.”
- Which were the greatest challenges for MW-synthesis to work?
“Microwaves had a reputation of damaging resins and creating optical isomers of the peptides. My doctoral candidate heard these rumors at several conferences, and that really challenged us to try it. Our resin turned out fine, the technique was fast and we had no problems at all with racemization. We could show clean NMR-spectra to back this up.”
- Describe peptide lab reality in the early 2000’s.
“People were experimenting with kitchen microwave ovens and making their own reaction vials. Temperature control was hopeless, and three or four times a day a vial would explode. Synthetic chemistry was highly manual – my doctoral candidate constructed his own “synthesis robot” using an electric drill which rotated the vials and stirred the reagents. After about two hours of reaction he would stop, remove the vials, filter, wash, add the next reagent and start the cycle again.”
- Which are the greatest improvements since then?
“Automation has come a long way. We can load the system and go home for the night. Generally, temperature control has improved significantly and vial explosions are much less frequent.”
- So what is on the peptide chemist’s wish-list today?
"Well, we can easily make our peptides, but the greatest problem today is purification. The biggest peptide we synthesized had 42 amino acids. It took a couple of days to synthesize but almost three months to purify! So maximum yield in each step is essential, and microwaves have been of great benefit here."
From the Personal Chemistry (now Biotage) Smith Synthesizer through to the Biotage® Initiator and now the current range of dedicated microwave peptide synthesizers such as the new Initiator+ Alstra, Biotage continues to provide tools for the global peptide community to enable the rapid synthesis of difficult and standard peptides in higher purity and yield.
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