-Silylated Diazoalkynes: New Tools for Bioconjugation of Proteins

alpha-Silylated diazoalkynes are stabilized diazo compounds that can selectively react with carboxylic residues in buffered aqueous media. In-situ fluoride induced desilylation increases this reactivity, leading to a very fast reaction. Application to the selective functionalization of RNase A, followed by post-functionalization using click chemistry, is described. These new reagents expand the toolbox for native protein modification at carboxylic residues. Bi-functionnal reagents bearing a Si-stabilized diazo function and a terminal alkyne can react with peptides or protein selectively at carboxylic residues in buffered aqueous media. A dramatic kinetic improvement of the conjugation is observed by in-situ fluoride-induced desilylation. Post-functionalization using click chemistry enables a late stage flexible diversification of the alkyne moiety. image