Macrocyclic bifunctional chelating agents
Assignee501 Regents of the University of California
InventorsClaude F. Meares, Sally J. DeNardo, William C. Cole, Min K. Mol
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Abstract
A copper chelate conjugate which is stable in human serum. The conjugate includes the copper chelate of a cyclic tetraaza di-, tri-, or tetra-acetic acid, a linker attached at one linker end to a ring carbon of the chelate, and a biomolecule joined at the other end of the linker. The conjugate, or the linker-copper chelate compound used in forming the conjugate, are designed for use in diagnostic and therapeutic applications which involve Cu(II) localization via the systemic route.
Claims14
A copper chelate conjugate for diagnostic or therapeutic applications which involve Cu(II) localization via the systemic route, comprising:
- a Cu(II) chelate of a bifunctional macrocyclic polyamine having the form:
- ##STR3## where k, l, m, and n=1-4, and at least two of R.sub.1 -R.sub.4 are --CH.sub.2 CO.sub.2.sup.- acid groups, the remainder are --CH.sub.2 CO.sub.2.sup.- or --H, L is a linker attached at one end to a ring carbon in the polyamine, and having at its other end, a chemically reactive group capable of reacting with a biomolecule, to form a chemical linkage therewith, and CH.sub.2(1) indicates that the ring carbon to which the linker is attached has only one hydrogen, and
- chemically linked to the linker, a biomolecule selected from the group consisting of antibodies, antibody fragments, serum proteins, and bleomycin.
A method of preparing Cu(II) for use in diagnostic and therapeutic applications which involve Cu(II) localization via the systemic route, comprising
- preparing a bifunctional polyamine macrocycle having the form:
- ##STR4## where k, l, m, and n=1-4, and at least two of R.sub.1 -R.sub.4 are --CH.sub.2 CO.sub.2.sup.- acid groups, the remainder are --CH.sub.2 CO.sub.2.sup.- or --H, L is a linker attached at one end to a ring carbon in the polyamine, and having at its other end, a chemically reactive group capable of reacting with a biomolecule, to form a chemical linkage therewith, and CH.sub.2(1) indicates that the ring carbon to which the linker is attached has only one hydrogen, and
- reacting the linker with a biomolecule selected from the group consisting of antibodies, antibody fragments, serum proteins, and and bleomycin, under conditions which are effective to couple the biomolecule covalently to the free end of the linker group, to form a macrocycle/biomolecule conjugate;
- and
- adding a Cu(II) salt to the macrocycle, prior to or after said reacting, to form a copper chelate of the macrocycle.
The use of a bifunctional cyclic tetraaza di-, tri-, or tetra-acetic acid copper chelate compound of the form:
- ##STR5## where k, l, m, and n=1-4, and at least two of R.sub.1 -R.sub.4 are --CH.sub.2 CO.sub.2.sup.- acid groups, the remainder are --CH.sub.2 CO.sub.2.sup.- or --H, L is a linker attached at one end to a ring carbon in the polyamine, and having at its other end, a chemically reactive group capable of reacting with a biomolecule, to form a chemical linkage therewith, and CH.sub.2(1) indicates that the ring carbon to which the linker is attached has only one hydrogen, for diagnostic and therapeutic applications which involve Cu(II) localization via the systemic route.
Dependencies are inferred from the claim text.