Allenamides : synthesis and applications as orthogonal handle for protein modification and bioconjugation

Abstract

This work deals with an important strategy of carrying out chemical reactions in biological systems through “orthogonal handles” where two functional groups react with each other selectively without reacting with other potentially reactive functional groups. We have reported the first synthesis of unsubstituted N-allenamides and their reaction with cysteine thiol in aqueous solution as a means to target cysteine residues in totally unprotected peptides and proteins. Reaction is mild, fast, selective and irreversible, giving products which are stable in human serum. We have demonstrated the application of this strategy in selective labelling of proteins using fluorescent dyes, preparing folate-dye conjugates for imaging of FR positive cancer cell lines and surface modification of silica nanoparticles. We are currently trying to exploit this strategy in preparing some useful conjugates with monoclonal antibodies and some future works are also in pipeline.