Toward Semisynthetic Lipoproteins by Convergent Strategies Based on Click and Ligation Chemistry

Abstract

A new convergent strategy is proposed for the semisynthesis of C-terminally lipidated proteins that is based on the copper(I)-catalyzed 1,3-dipolar cycloaddition of terminal alkynes in synthetic peptides to dimyristoylphosphatidylethanol azide followed by native chemical ligation (NCL) or expressed protein ligation (EPL) of the lipopeptide with synthetic or expressed polypeptide thioesters.