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US 5,326,856 AGranted
Bifunctional isothiocyanate derived thiocarbonyls as ligands for metal binding
AssigneeCytogen Corporation
InventorsDaniel J. Coughlin, Benjamin A. Belinka, Jr.
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Abstract
This invention relates to chelating agents useful for coupling metal ions to biologically active molecules. In particular, isothiocyanate derived thiocarbonyls for chelating metals such as technetium are provided that can be conjugated to a targeting molecule such as an antibody, a peptide or a protein.
Claims45
A chelating agent of the formula:
- ##STR11## in which NHCSNHR is in the 2,3- or 3,4-positions, and R is H or a substituent of the general formula:
- R=--(NH).sub.a (CH.sub.2).sub.b CY(NH).sub.d (CH.sub.2).sub.e --Z
- in which
- a=0 or 1;
- b=0-10;
- CY is C.dbd.S, C.dbd.O or CH.sub.2 ;
- d=0-2;
- e=1-10;
- Z=is H, N(R').sub.3.sup.+ X.sup.-, SO.sub.3 H, CO.sub.2 H, OH, H.sub.2 PO.sub.3 ;
- in which X.sup.- is a counterion such as a halide or an acid salt and R' is a C.sub.1 to C.sub.4 lower alkyl;
- and
- L comprises a reactive linker group selected from the group consisting of a primary amine, hydrazide, acid hydrazide, thioacid hydrazide, semicarbazide, thiosemicarbazide, reactive disulfide group, p-mercuribenzoate group, maleimide group, carboxylic acid, a carboxylic acid ester, an isothiocyanate, and succinate.
9 more elements
A chelating agent of the formula:
- ##STR12## in which the NHCSNHR groups are in the 2,4- or 3,5-positions;
- and R is hydrogen or a substituent of the general formula:
- R=--(NH).sub.a (CH.sub.2).sub.b CY(NH).sub.d (CH.sub.2).sub.e --Z
- in which
- a=0 or 1;
- b=0-10;
- CY is C.dbd.S, C.dbd.O or CH.sub.2 ;
- d=0-2;
- e=1-10;
- Z=is H, N(R').sub.3.sup.+ X.sup.-, SO.sub.3 H, CO.sub.2 H, OH, H.sub.2 PO.sub.3 ;
- in which X.sup.- is a counterion such as a halide or an acid melt and R' is a C.sub.1 to C.sub.4 lower alkyl;
- and
- L comprises a reactive linker group selected from the group consisting of a primary amine, hydrazide, acid hydrazide, thioacid hydrazide, semicarbazide, thiosemicarbazide, reactive disulfide group, p-mercuribenzoate group, maleimide group, carboxylic acid, a carboxylic acid ester, an isothiocyanate, and succinate.
10 more elements
The chelating agent of claim 39 in which R is:
- --(NH).sub.a CY(CH.sub.2).sub.e Z
- in which
- a=0-2,
- e=0-10,
- CY is C.dbd.S, C.dbd.O or CH.sub.2 ;
- and
- Z is H, N(R').sub.3.sup.+ X.sup.-, SO.sub.3 H, CO.sub.2 H, OH, H.sub.2 PO.sub.3 ;
- in which X.sup.- is a counterion such as a halide or an acid salt and R' is a C.sub.1 to C.sub.4 lower alkyl.
5 more elements
Dependencies are inferred from the claim text.