Insertion of organometallic moieties into peptides and peptide nucleic acids using alternative “click” strategies

Abstract

The insertion of metal complexes in biologically active systems is of great interest in view of diagnostic and therapeutic applications as well as a precious tool to unveil biological mechanisms. Optimization of safe and biocompatible reactions is critical to achieve high functionalization efficiency. Herein we present the application of two modified versions of copper-catalyzed azide–alkyne cycloaddition (click) chemistry, namely a one-pot diazotransfer + azide–alkyne cycloaddition (one-pot click) and a copper-free photoactivated tetrazole–alkene cycloaddition (photoclick), for derivatization of peptides and peptide nucleic acids (PNAs) with ferrocene and cymantrene moieties. These metal fragments were chosen for their possible exploitation as redox and IR probes. We could demonstrate that one-pot click enables for efficient functionalization of propargyl-glycine and an alkyne-containing peptide with an amino-containing cymantrene precursor. In addition, we could show that photoclick allows for the insertion of maleimido-ferrocene into a peptide and a PNA sequence containing a tetrazole moiety.