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Bifunctional chelating agent for the design and development of site specific radiopharmaceuticals and biomolecule conjugation strategy

Patent ·
OSTI ID:1174538
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There is provided a method of labeling a biomolecule with a transition metal or radiometal in a site specific manner to produce a diagnostic or therapeutic pharmaceutical compound by synthesizing a P.sub.2 N.sub.2 -bifunctional chelating agent intermediate, complexing the intermediate with a radio metal or a transition metal, and covalently linking the resulting metal-complexed bifunctional chelating agent with a biomolecule in a site specific manner. Also provided is a method of synthesizing the --PR.sub.2 containing biomolecules by synthesizing a P.sub.2 N.sub.2 -bifunctional chelating agent intermediate, complexing the intermediate with a radiometal or a transition metal, and covalently linking the resulting radio metal-complexed bifunctional chelating agent with a biomolecule in a site specific manner. There is provided a therapeutic or diagnostic agent comprising a --PR.sub.2 containing biomolecule.

Research Organization:
The Curators of the University of Missouri, Columbia, MO, (United States)
Sponsoring Organization:
USDOE
DOE Contract Number:
FG02-89ER60875
Assignee:
The Curators of the University of Missouri (Columbia, MO)
Patent Number(s):
6,635,235
Application Number:
09/602,487
OSTI ID:
1174538
Country of Publication:
United States
Language:
English

References (5)

Synthesis of Phosphine−Rhodium Complexes Attached to a Standard Peptide Synthesis Resin journal January 1996
Versatile Building Block for the Synthesis of Phosphine-Containing Peptides: The Sulfide of Diphenylphosphinoserine journal May 1994
99m Tc Labeling of Highly Potent Small Peptides journal September 1997
In vitro and in vivo characterization of novel water-soluble dithio-bisphosphine 99mTc complexes journal October 1997
Syntheses and Characterization of Chemically Flexible, Water-Soluble Dithio−Bis(phosphine) Compounds:  (HOH 2 C) 2 P(CH 2 ) 2 S(CH 2 ) 3 S(CH 2 ) 2 P(CH 2 OH) 2 , (HOH 2 C) 2 PCH 2 CH 2 S(CH 2 ) 4 SCH 2 CH 2 P(CH 2 OH) 2 , and (HOH 2 C) 2 PCH 2 CH 2 CH 2 S(CH 2 ) 3 SCH 2 CH 2 CH 2 P(CH 2 OH) 2 . Systematic Investigation of the Effect of Chain Length on the Coordination Chemistry of Rhenium(V). X-ray Crystal Structures of [ReO 2 (HOH 2 C) 2 P(CH 2 ) 2 S(CH 2 ) 3 S(CH 2 ) 2 P(CH 2 OH) 2 ] 2 (Cl) 2 , [ReO 2 (HOH 2 C) 2 P(CH 2 ) 2 S(CH 2 ) 4 S(CH 2 ) 2 P-(CH 2 OH) 2 ] 2 (ReO 4 - ) 2 , and [ReO 2 (HOH 2 C) 2 P(CH 2 ) 3 S(CH 2 ) 3 S(CH 2 ) 3 P(CH 2 OH) 2 ](Cl) journal August 1997

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY