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

• Published in: Chemistry : a European journal Vol. 20; no. 26; pp. 8116 - 8128
• Main Authors: Miyazaki, Ayako, Asanuma, Miwako, Dodo, Kosuke, Egami, Hiromichi, Sodeoka, Mikiko
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 23-06-2014; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Alkynes; Alkynes - chemistry; Amines; Amino acids; Chemistry; Cobalt; Cobalt - chemistry; Dilution; Enrichment; Molecular Structure; peptides; Peptides - chemistry; Polymers; Resins; solid-phase synthesis; peptides; cobalt; solid-phase synthesis; alkynes
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201400056

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.
Catch and release: The specific enrichment of alkyne‐tagged molecules has been achieved by using cobalt beads. A cobalt complex bound to a resin was found to selectively “catch” a propargyl carbamate tag under dilute aqueous conditions (see scheme). Upon acidic treatment of the alkyne–cobalt complex, the Nicholas reaction was induced to “release” an amine. Studies using an alkyne‐tagged dipeptide proved its compatibility with various amino acids and peptides under highly dilute conditions.