Bifunctional chelators for copper radiopharmaceuticals: the synthesis of [Cu(ATSM)-amino acid] and [Cu(ATSM)-octreotide] conjugates.
Two new bifunctional chelators that are derivatives of the bis(thiosemicarbazone) ATSMH(2) proligand have been prepared, one with two phenyl carboxylate substituents on the exocyclic nitrogens (L(1)H(2)) and one with a single phenyl carboxylate (L(2)H(2)). The new ligands have been characterised by NMR spectroscopy, mass spectrometry and in the case of L(1)H(2) by X-ray crystallography. The copper, nickel and zinc complexes of the new ligands have been synthesised and characterised. Electrochemical measurements show that the copper(II) complexes undergo a reversible reduction attributable to a Cu(II)/Cu(I) process. The new proligands have been tethered to the N-alpha-Boc-protected amino acids lysine and ornithine using solution and solid phase methods. The new amino acid conjugates form copper complexes and the complexes have been characterised by mass spectrometry and electronic spectroscopy. The bifunctional chelator L(2)H(2) has been conjugated to the tumour targeting peptide octreotide and the new ATSMH(2)-octreotide conjugate and its copper complex have been characterized by mass spectrometry. These new systems have the potential to be used for new targeted copper radiopharmaceuticals for imaging and therapy.
Cowley
Andrew R
AR
Chemical Crystallography Laboratory, University of Oxford, 12 Mansfield Road, Oxford, UK OX1 3TA.
Dilworth
Jonathan R
JR
Donnelly
Paul S
PS
Heslop
Julia M
JM
Ratcliffe
Steven J
SJ
D000596:Amino Acids / Q000737:chemistry*; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D015282:Octreotide / Q000031:analogs & derivatives* / Q000737:chemistry*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000737:chemistry*
D000596:Amino Acids; D002614:Chelating Agents; D008024:Ligands; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D003300:Copper; D015282:Octreotide