Methods and compositions for radiohalogen protein labeling

摘要

Methods and compositions are provided for labeling proteins with radiohalogen-label reagents. Radiohalogen-labeled proteins may be used for imaging studies, as therapeutics and in diagnostic tests. The [125I] HIP-DOTA label reagent 6 is prepared by an efficient and convenient process.;

主权项

1. A radiohalogen-labeling reagent having the structure: wherein Hal is a radiohalide isotope selected from 123I, 124I, 125I, 131I, and 211At; L is a linker selected from —(C1-C12 alkylene)-C(O)NR—(C1-C12 alkylene)-, —(C1-C12 alkylene)-C(O)NR—(C1-C12 alkylene)O—, —(C1-C12 alkylene)-C(O)NR—(C1-C12 alkylene)-C(O)CH2—, —(C1-C12 alkylene)-C(O)N(R)—, —(C1-C12 alkylene)-C(O)NR—(C2-C8 alkenylene)-, —(C1-C12 alkylene)-C(O)NR—(C2-C8 alkynylene)-, —(C1-C12 alkylene)-C(O)NR(CH2CH2O)n—, —(C1-C12 alkylene)-C(O)—, —(C1-C12 alkylene)-C(O)NR(CH2CH2O)nCH2C(O)—, and —(C1-C12 alkylene)-C(O)NR(CH2CH2O)nCH2—, where n is 1 to 6, R is H, C1-C12 alkyl, or C6-C20 aryl, and alkylene, alkenylene, alkynylene, alkyl, and aryl are optionally substituted with one or more groups selected from F, Cl, Br, I, —CH3, —CH2CH3, —CH(CH3)2, —CH2CH(CH3)2, —CH2NH2, —CH2CH2NH2, —CH2CHCH2NH2, —CH2CH(CH3)NH2, —CH2OH, —CH2OCH3, —CH2CH2OH, —CH2CH2OCH3, —C(CH3)2OH, —CH(OH)CH(CH3)2, —C(CH3)2CH2OH, —CH2CH2SO2CH3, —CN, —CF3, —CO2H, —COCH3, —CO2CH3, —CO2C(CH3)3, —COCH(OH)CH3, —CONH2, —CONHCH3, —CON(CH3)2, —C(CH3)2CONH2, —NO2, —NH2, —NHCH3, —N(CH3)2, —NHCOCH3, —N(CH3)COCH3, —NHS(O)2CH3, —N(CH3)C(CH3)2CONH2, —N(CH3)CH2CH2S(O)2CH3, ═O, —OH, —OCH3, —OP(O)3, —S(O)2N(CH3)2, —S(O)3, —SCH3, and —S(O)2CH3; and E is a reactive functional group selected from maleimide, thiol, amino, bromide, bromoacetamido, p-toluenesulfonate, iodide, hydroxyl, carboxyl, aldehyde, pyridyl disulfide, N-hydroxysuccinimide, azido, isocyanato, isothiocyanato, and phosphoramidite.