Design and synthesis of amidine-type peptide bond isosteres: application of nitrile oxide derivatives as active ester equivalents in peptide and peptidomimetics synthesis.

• Inokuchi, Eriko

• Yamada, Ai

• Hozumi, Kentaro

• Tomita, Kenji

• 大石, 真也

• Ohno, Hiroaki

• Nomizu, Motoyoshi

• 藤井, 信孝

抄録

Amidine-type peptide bond isosteres were designed based on the substitution of the peptide bond carbonyl (C=O) group with an imino (C=NH) group. The positively-charged property of the isosteric part resembles a reduced amide-type peptidomimetic. The peptidyl amidine units were synthesized by the reduction of a key amidoxime (N-hydroxyamidine) precursor, which was prepared from nitrile oxide components as an aminoacyl or peptidyl equivalent. This nitrile oxide-mediated C-N bond formation was also used for peptide macrocyclization, in which the amidoxime group was converted to peptide bonds under mild acidic conditions. Syntheses of the cyclic RGD peptide and a peptidomimetic using both approaches, and their inhibitory activity against integrin-mediated cell attachment, are presented.

収録刊行物

• Organic & biomolecular chemistry

  Organic & biomolecular chemistry 9 (9), 3421-3427, 2011-05-07

  Royal Society of Chemistry

キーワード

• Amidines/chemistry
• Amino Acids/chemistry
• Drug Design
• Esters/chemistry
• Ions/chemistry
• Molecular Structure
• Nitriles/chemistry
• Oxides/chemistry
• Peptides/chemical synthesis
• Peptidomimetics/chemical synthesis

詳細情報

• CRID: 1050282810711372416
• NII論文ID: 120004225660
• NII書誌ID: AA1168650X
• ISSN: 14770520
• HANDLE: 2433/156967
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles