title: A bioorthogonal quadricyclane ligation.
abstract: New additions to the bioorthogonal chemistry compendium can advance biological research by enabling multiplexed analysis of biomolecules in complex systems. Here we introduce the quadricyclane ligation, a new bioorthogonal reaction between the highly strained hydrocarbon quadricyclane and Ni bis(dithiolene) reagents. This reaction has a second-order rate constant of 0.25 M(-1) s(-1), on par with fast bioorthogonal reactions of azides, and proceeds readily in aqueous environments. Ni bis(dithiolene) probes selectively labeled quadricyclane-modified bovine serum albumin, even in the presence of cell lysate. We have demonstrated that the quadricyclane ligation is compatible with, and orthogonal to, strain-promoted azide-alkyne cycloaddition and oxime ligation chemistries by performing all three reactions in one pot on differentially functionalized protein substrates. The quadricyclane ligation joins a small but growing list of tools for the selective covalent modification of biomolecules.
authors.affiliation: Department of Chemistry and Howard Hughes Medical Institute, University of California, Berkeley, California 94720, United States.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Sletten
authors.forename: Carolyn R
authors.initials: CR
authors.lastname: Bertozzi
mesh_terms: D000480:Alkynes / Q000737:chemistry; D000818:Animals; D001386:Azides / Q000737:chemistry; D001952:Bridged-Ring Compounds / Q000737:chemistry*; D002417:Cattle; D003500:Cyclization; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry
chemical_list: D000480:Alkynes; D001386:Azides; D001952:Bridged-Ring Compounds; D009942:Organometallic Compounds; D012710:Serum Albumin, Bovine; C513530:quadricyclane