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Synthesis of Insulin-desB30 Analogs via an Enzymatically Removable N-Terminal Solubilizing Tag
Yuankun Dao1, Terra Lin1, Ngoc Le Bich Tran1
1Department of Pediatrics, Division of Diabetes and Endocrinology, Stanford University, Palo Alto, California 94304, United States.
None:
Chemical synthesis enables rapid access to designed insulin analogs, but the efficiency is hindered by the insulin A-chain's poor solubility. We report a streamlined route using direct Fmoc-SPPS of a native A chain aided by a temporary polylysine solubility tag removable by Lys-C under mild aqueous conditions. The workflow improves isolation, folding, and chain combination and generalizes to difficult targets (A16Pro mutant insulin, methyl-ketone A6-A11 surrogate, four-disulfide insulin), delivering high-purity products.
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