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Issue 9, 2011
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Design and synthesis of amidine-type peptide bond isosteres: application of nitrile oxide derivatives as active ester equivalents in peptide and peptidomimetics synthesis

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Abstract

Amidine-type peptide bond isosteres were designed based on the substitution of the peptide bond carbonyl (C[double bond, length as m-dash]O) group with an imino (C[double bond, length as m-dash]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.

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

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Publication details

The article was received on 17 Dec 2010, accepted on 16 Feb 2011 and first published on 22 Feb 2011


Article type: Paper
DOI: 10.1039/C0OB01193B
Citation: Org. Biomol. Chem., 2011,9, 3421-3427
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    Design and synthesis of amidine-type peptide bond isosteres: application of nitrile oxide derivatives as active ester equivalents in peptide and peptidomimetics synthesis

    E. Inokuchi, A. Yamada, K. Hozumi, K. Tomita, S. Oishi, H. Ohno, M. Nomizu and N. Fujii, Org. Biomol. Chem., 2011, 9, 3421
    DOI: 10.1039/C0OB01193B

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