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Updated: Jun 28, 2025
Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
Challenges with the Synthesis of a Macrocyclic Thioether Peptide: From Milligram to Multigram Using Solid Phase
James Kempson1, Rulin Zhao1, Joseph Pawluczyk1
1Research and Early Development, Bristol-Myers Squibb Company, Princeton, New Jersey 08543-4000, United States.
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We describe an optimization and scale-up of the 45-membered macrocyclic thioether peptide BMS-986189 utilizing solid-phase peptide synthesis (SPPS). Improvements to linear peptide isolation, macrocyclization, and peptide purification were demonstrated to increase the throughput and purification of material on scale and enabled the synthesis and purification of >60 g of target peptide. Taken together, not only these improvements resulted in a 28-fold yield increase from the original SPPS approach, but also the generality of this newly developed SPPS purification sequence has found application in the synthesis and purification of other macrocyclic thioether peptides.
