Macrobicyclic Cage Amine Ligands for Copper Radiopharmaceuticals: A Single Bivalent Cage Amine Containing Two Lys(3)-bombesin Targeting Peptides
AuthorMa, MT; Cooper, MS; Paul, RL; Shaw, KP; Karas, JA; Scanlon, D; White, JM; Blower, PJ; Donnelly, PS
Source TitleINORGANIC CHEMISTRY
PublisherAMER CHEMICAL SOC
University of Melbourne Author/sSCANLON, DENIS; White, Jonathan; Donnelly, Paul; MA, MICHELLE; Karas, John
Document TypeJournal Article
CitationsMa, MT; Cooper, MS; Paul, RL; Shaw, KP; Karas, JA; Scanlon, D; White, JM; Blower, PJ; Donnelly, PS, Macrobicyclic Cage Amine Ligands for Copper Radiopharmaceuticals: A Single Bivalent Cage Amine Containing Two Lys(3)-bombesin Targeting Peptides, INORGANIC CHEMISTRY, 2011, 50 (14), pp. 6701 - 6710
Access StatusThis item is currently not available from this repository
ARC Grant codeARC/LE0775481
C1 - Journal Articles Refereed
The synthesis of new cage amine macrobicyclic ligands with pendent carboxylate functional groups designed for application in copper radiopharmaceuticals is described. Reaction of [Cu((NH(2))(2)sar)](2+) (sar = 3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane) with either succinic or glutaric anhydride results in selective acylation of the primary amine atoms of [Cu((NH(2))(2)sar)](2+) to give derivatives with either one or two aliphatic carboxylate functional groups separated from the cage amine framework by either a four- or five-atom linker. The Cu(II) serves to protect the secondary amine nitrogen atoms from acylation, and can be removed to give the free ligands. The newly appended carboxylate functional groups can be used as sites of attachment for cancer-targeting peptides such as Lys(3)-bombesin. The synthesis of the first dimeric sarcophagine-peptide conjugate, possessing two Lys(3)-bombesin peptides tethered to a single cage amine, is presented. This species has been radiolabeled with copper-64 at ambient temperature and there is minimal dissociation of Cu(II) from the conjugate even after two days of incubation in human serum.
KeywordsBioinorganic Chemistry; Transition Metal Chemistry; Inorganic Chemistry not elsewhere classified; Proteins and Peptides; Organic Chemical Synthesis; Expanding Knowledge in the Chemical Sciences
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