Compositions and methods for quadricyclane modification of biomolecules
AssigneeThe Regents of the University of California
InventorsEllen May Sletten, Carolyn Ruth Bertozzi
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Abstract
The present disclosure features a strain-promoted [2+2+2] reaction that can be carried out under physiological conditions. In general, the reaction involves reacting a pi-electrophile with a low lying LUMO with a quadricyclane on a biomolecule, generating a covalently modified biomolecule. The selectivity of the reaction and its compatibility with aqueous environments provides for its application in vivo and in vitro. The reaction is compatible with modification of living cells. In certain embodiments, the pi-electrophile can comprise a molecule of interest that is desired for delivery to a quadricyclane-containing biomolecule via [2+2+2] reaction.
Claims14
A compound
- of the formula:
- wherein
- R1, R2, R3, R4, and R5 are optional linkers;
- Z1, Z2, Z3, Z4, and Z5 are independently selected from hydrogen and a biomolecule;
- wherein at least one of Z1, Z2, Z3, Z4, and Z5 is a biomolecule.
A method for chemoselective modification of a biomolecule comprising a quadricyclane, the method comprising:
- reacting a quadricyclane in a quadricyclane-containing biomolecule with a pi electrophile compound selected from a metal bis(dithiolene) compound, an azo compound, an alkynyl compound, an alkenyl compound and a ketone compound,
- wherein said reacting produces a conjugate between the quadricyclane of the quadracyclane-containing biomolecule and the pi electrophile compound.
Dependencies are inferred from the claim text.