A “Catch‐and‐Release” Protocol for Alkyne‐Tagged Molecules Based on a Resin‐Bound Cobalt Complex for Peptide Enrichment in Aqueous Media

Abstract

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.

Simple purification of small-molecule-labelled peptides via palladium enolate formation from β-ketoamide tags

“…Compared with previous results using a cobalt complex (Fig. 1b), 27,28 a relatively more efficient catch and release with shorter incubation time, milder acid treatment, and a longer model peptide were achieved in the present study.…”

Chemical reagents for the enrichment of modified peptides in MS-based identification

“…Next, the complex was released from resin upon acidic treatment. 27,52 When the ''catch-and-release'' experiment was carried out with a peptide mixture, non-alkyne-containing peptides were washed out from the resin and the remaining alkyne tagged peptides were enriched and further released from the resin (Fig. 7A).…”

“…2C and D). 26,27 This review focuses on the current progress in the development of chemical reagents for the enrichment of modified peptides in MS-based identification.…”

Modular synthetic strategy for N/C‐terminal protected amyloidogenic peptides

“…The synthesis was according to a previous report 10 with some modifications. A solution of benzoyl chloride (1.4 ml, 12.1 mmol) in THF (1.5 ml) was added to a mixture of L-asparagine monohydrate (1.50 g, 10 mmol) and Na 2 CO 3 (1.38 g, 10 mmol) in H 2 O (10 ml) and THF (1 ml) at 55 C. After stirring at 55 C for 1 h, the reaction mixture was cooled to room temperature, and 1 N HCl solution (10 ml) was added.…”