Chemistry. 2016 Jun 3. doi: 10.1002/chem.201601410. [Epub ahead of print]
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.
- 1Department of Chemistry, Indiana University Bloomington, 800 E. Kirkwood Avenue, Bloomington, Indiana, 47405, USA.
- 2Novo Nordisk Research Center Indianapolis, 5225 Exploration Drive, Indianapolis, Indiana, 46241, USA. firstname.lastname@example.org.
- 3Department of Chemistry, Indiana University Bloomington, 800 E. Kirkwood Avenue, Bloomington, Indiana, 47405, USA. email@example.com.