skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Biomolecule conjugation strategy using novel water-soluble phosphine-based chelating agents

Patent ·
OSTI ID:1174992
; ;

This invention describes a novel strategy to produce phosphine-functionalized biomolecules (e.g. peptides or proteins) for potential use in the design and development of site-specific radiopharmaceuticals for diagnosis or therapy of specific cancers. Hydrophilic alkyl phosphines, in general, tend to be oxidatively unstable. Therefore, incorporation of such phosphine functionalities on peptide (and other biomolecule) backbones, without oxidizing the P.sup.III centers, is difficult. In this context this discovery reports on a new technology by which phosphines, in the form of bifunctional chelating agents, can be directly incorporated on biomolecular backbones using manual synthetic or solid phase peptide synthesis methodologies. The superior ligating abilities of phosphine ligands, with various diagnostically (e.g. TC-99m) or therapeutically (e.g. Re186/188, Rh-105, Au-199) useful radiometals, coupled with the findings that the resulting complexes demonstrate high in vivo stability makes this approach useful in the development of radiolabeled biomolecules for applications in the design of tumor-specific radiopharmaceuticals.

Research Organization:
Univ. of Missouri, Columbia, MO (United States)
Sponsoring Organization:
USDOE
DOE Contract Number:
FG0289ER60875
Assignee:
University Of Missouri
Patent Number(s):
6,780,397
Application Number:
09/386,657
OSTI ID:
1174992
Country of Publication:
United States
Language:
English

References (9)

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
In vitro and in vivo characterization of a 99mTc complex with tris(hydroxymethyl)phosphine (THP) journal July 1996
Synthesis and Coordination Chemistry of the First Water-Soluble Dithio−Bis(phosphine) Ligands [(HOH 2 C) 2 P(CH 2 ) 2 S−X−S(CH 2 ) 2 P(CH 2 OH) 2 ] (X = (CH 2 ) 3 or C 6 H 4 ). X-ray Crystal Structure of [Pd(HOH 2 C) 2 P(CH 2 ) 2 S(CH 2 ) 3 S(CH 2 ) 2 P(CH 2 OH) 2 ](Cl) 2 1 journal April 1997
Recent Developments in Peptide Drug Delivery to the Brain journal July 1992
Pharmacologic effects in vivo in brain by vector-mediated peptide drug delivery. journal April 1993
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
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

Similar Records

Related Subjects

59 BASIC BIOLOGICAL SCIENCES