Chemical Synthesis of Human Insulin-Like Peptide-6

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• 作者：Fangzhou Wu ; Dr. John P. Mayer ; Dr. Alexander N. Zaykov ; Dr. Fa Zhang ; Dr. Fa Liu and Prof. Richard D. DiMarchi
• 刊名：Chemistry - A European Journal
• 出版年：2016
• 出版时间：July 4, 2016
• 年：2016
• 卷：22
• 期：28
• 页码：9777-9783
• 全文大小：1181K
• ISSN：1521-3765

文摘

Human insulin-like peptide-6 (INSL-6) belongs to the insulin superfamily and shares the distinctive disulfide bond configuration of human insulin. In this report we present the first chemical synthesis of INSL-6 utilizing fluorenylmethyloxycarbonyl-based (Fmoc) solid-phase peptide chemistry and regioselective disulfide bond construction protocols. Due to the presence of an oxidation-sensitive tryptophan residue, two new orthogonal synthetic methodologies were developed. The first method involved the identification of an additive to suppress the oxidation of tryptophan during iodine-mediated S-acetamidomethyl (Acm) deprotection and the second utilized iodine-free, sulfoxide-directed disulfide bond formation. The methodologies presented here offer an efficient synthetic route to INSL-6 and will further improve synthetic access to other multiple-disulfide-containing peptides with oxidation-sensitive residues.