Sieving P F, Watson A D, Rocklage S M
Salutar, Incorporated, Sunnyvale, California 94086.
Bioconjug Chem. 1990 Jan-Feb;1(1):65-71. doi: 10.1021/bc00001a008.
The gadolinium complexes of poly-L-lysine-poly(diethylenetriamine-N,N,N',N",N"-pentaacetic acid) (Gd-PL-DTPA) and poly-L-lysine-poly(1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetr aacetic acid) (Gd-PL-DOTA) and their conjugates with human serum albumin (HSA) have been prepared and characterized. Poly-L-lysine (PL, degree of polymerization approximately 100) was N-acylated with a mixed anhydride of the chelating ligand (DTPA or DOTA). Sixty to ninety chelating groups per molecule of PL could be attached in this way. Following purification of the polychelate by size-exclusion chromatography, the gadolinium complexes were prepared by standard methods and conjugated to HSA with heterobifunctional cross-linking reagents. The molar relaxities of these macromolecular species were 2-3-fold higher than those of the corresponding monomeric metal complexes [( Gd(DTPA)] and [Gd(DOTA)]). The conjugation conditions were optimized to produce conjugates containing 60-90 metal centers per molecule of HSA (ca. one polychelate per protein).
已制备并表征了聚-L-赖氨酸-聚（二亚乙基三胺-N,N,N',N",N"-五乙酸）（钆-聚-L-赖氨酸-二乙三胺五乙酸，Gd-PL-DTPA）和聚-L-赖氨酸-聚（1,4,7,10-四氮杂环十二烷-N,N',N",N"'-四乙酸）（钆-聚-L-赖氨酸-四氮杂环十二烷四乙酸，Gd-PL-DOTA）的钆配合物及其与人血清白蛋白（HSA）的缀合物。聚-L-赖氨酸（PL，聚合度约为100）用螯合配体（DTPA或DOTA）的混合酸酐进行N-酰化。通过这种方式，每个PL分子可以连接60至90个螯合基团。通过尺寸排阻色谱法纯化多螯合物后，用标准方法制备钆配合物，并用异双功能交联剂与HSA缀合。这些大分子物质的摩尔弛豫率比相应的单体金属配合物[钆（二乙三胺五乙酸）]和[钆（四氮杂环十二烷四乙酸）]高2至3倍。优化了缀合条件，以产生每分子HSA含有60至90个金属中心的缀合物（每个蛋白质约一个多螯合物）。
