Convergent synthesis of aminomethylene peptidomimetics.
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.
Davenport Research Laboratories, Department of Chemistry, University of Toronto, Toronto, Ontario, Canada.
Naila
N
Assem
Andrei K
AK
Yudin
D000577:Amides / Q000737:chemistry*; D001388:Aziridines / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D015394:Molecular Structure; D009842:Oligopeptides; D057786:Peptidomimetics / Q000138:chemical synthesis* / Q000737:chemistry*; D015202:Protein Engineering / Q000379:methods*; D055550:Protein Stability
D000577:Amides; D001388:Aziridines; C089417:L 739750; D009842:Oligopeptides; D057786:Peptidomimetics