title: Hydrophobic benzyl amines as supports for liquid-phase C-terminal amidated peptide synthesis: application to the preparation of ABT-510.
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.
authors.affiliation: Department of Applied Biological Chemistry, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo, 183-8509, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Matsumoto
authors.affiliation: Department of Applied Biological Chemistry, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo, 183-8509, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Department of Chemical Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo, 184-8588, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Department of Chemical Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo, 184-8588, Japan.|Department of Applied Physics, Aalto University School of Science, Puumiehenkuja 2, Aalto, 00076, Finland.
authors.forename: Esko I
authors.initials: EI
authors.lastname: Kauppinen
authors.affiliation: Department of Chemical Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo, 184-8588, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Kamiya
authors.affiliation: Department of Applied Biological Chemistry, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo, 183-8509, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Chiba
mesh_terms: D000588:Amines / Q000737:chemistry*; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D000588:Amines; D010455:Peptides
keywords: ABT-510; C-terminal amidation; epimerization; hydrophobic benzyl amine; soluble tag-assisted liquid-phase peptide synthesis