title: Preparation and characterization of paramagnetic polychelates and their protein conjugates.
abstract: 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).
authors.affiliation: Salutar, Incorporated, Sunnyvale, California 94086.
authors.forename: P F
authors.initials: PF
authors.lastname: Sieving
authors.forename: A D
authors.initials: AD
authors.lastname: Watson
authors.forename: S M
authors.initials: SM
authors.lastname: Rocklage
mesh_terms: D002614:Chelating Agents; D005682:Gadolinium / Q000737:chemistry*; D019786:Gadolinium DTPA; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D007202:Indicators and Reagents; D008024:Ligands; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D004369:Pentetic Acid / Q000138:chemical synthesis / Q000737:chemistry*; D011107:Polylysine / Q000138:chemical synthesis / Q000737:chemistry* / Q000031:analogs & derivatives; D011485:Protein Binding; D012709:Serum Albumin
chemical_list: D002614:Chelating Agents; D006571:Heterocyclic Compounds; D007202:Indicators and Reagents; D008024:Ligands; D009942:Organometallic Compounds; D012709:Serum Albumin; C069063:polylysine-(Gd-DOTA); C068674:polylysine-(Gd-DTPA); D011107:Polylysine; D004369:Pentetic Acid; D005682:Gadolinium; D019786:Gadolinium DTPA