A "catch-and-release" protocol for alkyne-tagged molecules based on a resin-bound cobalt complex for peptide...

The development of new and mild protocols for the specific enrichment of biomolecules is of significant interest from the perspective of chemical biology. A cobalt-phosphine complex immobilised on a solid-phase resin has been found to selectively bind to a propargyl carbamate tag, that is, "catch", under dilute aqueous conditions (pH 7) at 4 °C. Upon acidic treatment of the resulting resin-bound alkyne-cobalt complex, the Nicholas reaction was induced to "release" the alkyne-tagged molecule from the resin as a free amine. Model studies revealed that selective enrichment of the alkyne-tagged molecule could be achieved with high efficiency at 4 °C. The proof-of-concept was applied to an alkyne-tagged amino acid and dipeptide. Studies using an alkyne-tagged dipeptide proved that this protocol is compatible with various amino acids bearing a range of functionalities in the side-chain. In addition, selective enrichment and detection of an amine derived from the "catch and release" of an alkyne-tagged dipeptide in the presence of various peptides has been accomplished under highly dilute conditions, as determined by mass spectrometry.