Synthesis of Water-Soluble Scaffolds for Peptide Cyclization, Labeling, and Ligation

The synthesis and applications of water-soluble scaffolds that conformationally constrain side chain unprotected linear peptides containing two cysteines are described. These scaffolds contain a functionality with orthogonal reactivity to be used for labeling and ligation. This is illustrated by the chemical ligation of two dissimilar constrained peptides via oxime ligation or strain-promoted azide–alkyne cycloaddition in aqueous media