Hydrophobic benzyl amines as supports for liquid‐phase C‐terminal amidated peptide synthesis: application to the preparation of ABT‐510 |
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| Authors: | Emiko Matsumoto Yuko Fujita Yohei Okada Esko I. Kauppinen Hidehiro Kamiya Kazuhiro Chiba |
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| Affiliation: | 1. Department of Applied Biological Chemistry, Tokyo University of Agriculture and Technology, Tokyo, Japan;2. Department of Chemical Engineering, Tokyo University of Agriculture and Technology, Tokyo, Japan;3. Department of Applied Physics, Aalto University School of Science, Aalto, Finland |
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| Abstract: | C‐terminal amidation is one of the most common modification of peptides and frequently found in bioactive peptides. However, the C‐terminal modification must be creative, because current chemical synthetic techniques of peptides are dominated by the use of C‐terminal protecting supports. Therefore, it must be carried out after the removal of such supports, complicating reaction work‐up and product isolation. In this context, hydrophobic benzyl amines were successfully added to the growing toolbox of soluble tag‐assisted liquid‐phase peptide synthesis as supports, leading to the total synthesis of ABT‐510 ( 2 ). Although an ethyl amide‐forming type was used in the present work, different types of hydrophobic benzyl amines could also be simply designed and prepared through versatile reductive aminations in one step. The standard acidic treatment used in the final deprotection step for peptide synthesis gave the desired C‐terminal secondary amidated peptide with no epimerization. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd. |
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| Keywords: | hydrophobic benzyl amine soluble tag‐assisted liquid‐phase peptide synthesis C‐terminal amidation ABT‐510 epimerization |
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