Type-II diabetes, caused by chronic insulin resistance and a progressive decline in pancreatic b-cell function, affects over 150 million people worldwide [1]. The 37-mer Human islet amyloid polypeptide (IAPP) (Figure 1) or amylin, is a major contributor to the amyloid deposits found in the pancreases of patients with type-II diabetes [2,3]. Amylin is highly hydrophobic and prone to aggregation, making it a difficult peptide to synthesize in sufficient purity and yield [4]. To our knowledge, the application of heat during coupling reactions of amylin synthesis has not been fully assessed and may provide an advantage for reducing on resin aggregation. Automated on-resin disulfide bridge formation in amylin using Tl(tfa)3, a mild oxidant, can provide better yields and purities of the desired cyclic products, compared to other methods.
H-KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY-NH2
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Figure 1. Amylin structure.