摘要 |
The specification describes bioconjugates which comprise a bioactive agent and an organocobalt complex. The bioactive agent is covalently bonded directly or indirectly to the cobalt atom of the organocobalt complex. The bioactive agent is released from the bioconjugate by the cleavage of the covalent bond between the bioactive agent and the cobalt atom in the organocobalt complex. The cleavage may occur as a result of normal displacement by cellular nucleophiles or enzymatic action, but is preferably caused to occur selectively at a predetermined release site by application of an external signal. The external signal may be light or photoexcitation, i.e. photolysis, or it may be ultrasound, i.e. sonolysis. Further, if the photolysis takes places in the presence of a magnetic field surrounding the release site, the release of the bioactive agent into surrounding healthy tissue is minimized. Examples of targeting molecules include glucose, galactose, mannose, mannose 6phosphate, hormones (e.g., insulin, growth hormone, and the like), growth factors or cytokines (e.g., TGF-p, EGF, insulin-like growth factor, and the like), YEE(GalNAcAH)3 or derivatives, cobalamin, a-2 macroglobulins, asialoglycoprotein, albumin, texaphyrin, metallotexaphyrin, antibodies, antibody fragments (e.g., Fab), single-chain antibody variable region (scFv), transferrin, any vitamin and any coenzyme. The organocobalt complex is selected from the group consisting of an organo(pyridine)bis(dimethylglyoximato)cobalt, a corrinoid, or derivatives thereof.
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