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Nature Protocols | Protocol

Convergent synthesis of aminomethylene peptidomimetics

Journal name:
Nature Protocols
Volume:
7,
Pages:
1327–1334
Year published:
DOI:
doi:10.1038/nprot.2012.066
Published online

Abstract

This protocol describes a convergent synthesis of reduced amide bond peptidomimetics using thioacid-terminated peptides and aziridine-containing peptide conjugates. This approach could be used to produce peptides and proteins with modified backbones. The peptide conjugates are made using readily available aziridine aldehydes. The convergent synthesis of peptidomimetics is demonstrated through the preparation of long and short peptide fragments with an aminomethylene group incorporated within them. This transformation is amenable to the synthesis of peptides with reduced amide bonds at cysteine and alanine. The procedure describes the preparation of each component used and highlights the ease of synthesis of aminomethylene peptidomimetics, and takes about 3 d to complete.

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  1. A comparison of peptide and peptidomimetic linkages.
    Figure 1: A comparison of peptide and peptidomimetic linkages.
  2. Reductive amination with an aziridine aldehyde.
    Figure 2: Reductive amination with an aziridine aldehyde.
  3. Synthesis of thioacid functionality.
    Figure 3: Synthesis of thioacid functionality.
  4. Mechanism of peptidomimetic formation.
    Figure 4: Mechanism of peptidomimetic formation.
  5. Formation of a reduced peptide bond at alanine with the use of Raney nickel.
    Figure 5: Formation of a reduced peptide bond at alanine with the use of Raney nickel.
  6. HPLC of peptidomimetics containing a reduced peptide bond at cysteine (7) and at alanine (8).
    Figure 6: HPLC of peptidomimetics containing a reduced peptide bond at cysteine (7) and at alanine (8).

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Affiliations

  1. Davenport Research Laboratories, Department of Chemistry, University of Toronto, Toronto, Ontario, Canada.

    • Naila Assem &
    • Andrei K Yudin

Contributions

N.A. and A.K.Y. performed the work and wrote the manuscript.

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The authors declare no competing financial interests.

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