Bis(2-sulfanylethyl)amido Peptides Enable Native Chemical Ligati

Bis(2-sulfanylethyl)amido Peptides Enable Native Chemical Ligation at Proline and Minimize Deletion Side-Product Formation
Laurent Raibaut , Phillip Seeberger , and Oleg Melnyk *
Org. Lett., Article ASAP
DOI: 10.1021/ol402678a
Publication Date (Web): October 11, 2013
Copyright © 2013 American Chemical Society

Native chemical ligation of C-terminal peptidyl prolyl alkylthioesters with N-terminal cysteinyl peptides usually exhibits poor kinetic rates compared to other C-terminal amino acid residues. It is shown here that the reaction is accompanied by the formation of a deletion side product which is minimized by using a bis(2-sulfanylethyl)amido (SEA) thioester surrogate at a mildly acidic pH.