Chemoselective peptidomimetic ligation using thioacid peptides and aziridine templates.

Naila Assem, Aditya Natarajan, Andrei K Yudin

Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, Canada M5S 3H6.

Journal of the American Chemical Society 2010 Aug 18

filter terms:

Chemoselective peptidomimetic ligation has been made possible using thioacid peptides and NH aziridine-terminated amino acids and peptides. In the course of this reaction, a reduced amide bond is incorporated into the backbone of a peptide. This process enables incorporation of reduced cysteine, reduced substituted cysteine, reduced phenylalanine, and reduced alanine. Our method should be adaptable to other unnatural amino acid residues at the ligation site. Experiments aimed at evaluating the chemoselectivity of this process in the presence of competing thiol nucleophiles suggest high specificity at micromolar concentrations. This holds even in the presence of glutathione, which neutralizes xenobiotic electrophiles in cells.

Citation

Naila Assem, Aditya Natarajan, Andrei K Yudin. Chemoselective peptidomimetic ligation using thioacid peptides and aziridine templates. Journal of the American Chemical Society. 2010 Aug 18;132(32):10986-7