"How can I take a two hour purification using old-school chromatography, and shorten it?" was the question Dr. Aaron Muth at St. John's University in New York asked himself. "By using the Biotage Isolera, I could take it down to 10 or 15 minutes."

I have experimented a lot with disulfide rich peptides lately, finding conditions that work well for not only the linear synthesis, but also for on-resin cysteine oxidations.  Although simple scaffolds are useful for determining orthogonal protecting group removal and cysteine oxidation conditions, many of the peptides of interest today are much more complex – three or more disulfide bonds, and often head-to-tail cyclization.

In today’s post, I put to use three orthogonal protection strategies to optimize a fully automated synthesis of linaclotide.