Poster
Discovery of a New Bioorthogonal Pair for the Selective Labelling of Biomolecules
Jenna M. Mowat,a* Lukasz Frankiewicz,b Glenn A. Burleyaand Craig Jamiesona
aDepartment of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL. bGyros Protein Technologies Inc., 4675 South Coach Drive, Tucson, Arizona, 85714, USA
Bioorthogonal chemistry has been a growing area of chemical research since the term was first coined by Bertozzi in 2003 and since then it has greatly aided in the studies of biomolecules, such as peptides in a biological setting.
In this study, the development of a new biorthogonal pair for the dual labelling of peptide substrates is reported. Nitrile imines are highly reactive 1,3-dipoles which can be accessed
in situ following photolytic activation of 2,5-diaryl tetrazoles upon exposure to UV-light. The corresponding 1,3-dipole is known to participate in 1,3-dipolar cycloaddition processes with dipolarophiles. However, initial competition experiments have shown that nitrile imines will react preferentially with carboxylic acids even when in the presence of a dipolarophile, such as an alkyne. Any alkyne present may subsequently undergo CuAAC with an azide to yield the corresponding triazole product.
These findings were applied to the carboxylic acid present at the C-terminus of some biologically relevant peptides - including substance P and the enkephalins, by exposing them to a nitrile imine. The N-termini of the peptides were modified with an aromatic ynamine, which has high selectivity towards azides through CuAAC over traditional aliphatic alkynes yielding a peptide bearing two labels at either termini.
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