Biomolecule conjugation strategy using novel water-soluble phosphine-based chelating agents
Abstract
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.
- Inventors:
- Issue Date:
- Research Org.:
- Univ. of Missouri, Columbia, MO (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1174992
- Patent Number(s):
- 6780397
- Application Number:
- 09/386,657
- Assignee:
- University Of Missouri
- Patent Classifications (CPCs):
-
A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61K - PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
- DOE Contract Number:
- FG0289ER60875
- Resource Type:
- Patent
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Katti, Kattesh V., Gali, Hariprasad, and Volkert, Wynn A. Biomolecule conjugation strategy using novel water-soluble phosphine-based chelating agents. United States: N. p., 2004.
Web.
Katti, Kattesh V., Gali, Hariprasad, & Volkert, Wynn A. Biomolecule conjugation strategy using novel water-soluble phosphine-based chelating agents. United States.
Katti, Kattesh V., Gali, Hariprasad, and Volkert, Wynn A. Tue .
"Biomolecule conjugation strategy using novel water-soluble phosphine-based chelating agents". United States. https://www.osti.gov/servlets/purl/1174992.
@article{osti_1174992,
title = {Biomolecule conjugation strategy using novel water-soluble phosphine-based chelating agents},
author = {Katti, Kattesh V. and Gali, Hariprasad and Volkert, Wynn A.},
abstractNote = {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.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {2004},
month = {8}
}
Works referenced in this record:
99m Tc Labeling of Highly Potent Small Peptides
journal, September 1997
- Liu, Shuang; Edwards, D. Scott; Barrett, John A.
- Bioconjugate Chemistry, Vol. 8, Issue 5
In vitro and in vivo characterization of novel water-soluble dithio-bisphosphine 99mTc complexes
journal, October 1997
- Smith, C. J.; Li, N.; Katti, K. V.
- Nuclear Medicine and Biology, Vol. 24, Issue 7
In vitro and in vivo characterization of a 99mTc complex with tris(hydroxymethyl)phosphine (THP)
journal, July 1996
- Berning, D. E.; Katti, K. V.; Singh, P. R.
- Nuclear Medicine and Biology, Vol. 23, Issue 5
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
- Smith, C. Jeffrey; Reddy, V. Sreenivasa; Karra, Srinivasa R.
- Inorganic Chemistry, Vol. 36, Issue 9
Recent Developments in Peptide Drug Delivery to the Brain
journal, July 1992
- Pardridge, William M.
- Pharmacology & Toxicology, Vol. 71, Issue 1
Pharmacologic effects in vivo in brain by vector-mediated peptide drug delivery.
journal, April 1993
- Bickel, U.; Yoshikawa, T.; Landaw, E. M.
- Proceedings of the National Academy of Sciences, Vol. 90, Issue 7
Synthesis of Phosphine−Rhodium Complexes Attached to a Standard Peptide Synthesis Resin
journal, January 1996
- Gilbertson, Scott R.; Wang, Xifang; Hoge, Garrett S.
- Organometallics, Vol. 15, Issue 22
Versatile Building Block for the Synthesis of Phosphine-Containing Peptides: The Sulfide of Diphenylphosphinoserine
journal, May 1994
- Gilbertson, Scott R.; Chen, Guohua; McLoughlin, Margaret
- Journal of the American Chemical Society, Vol. 116, Issue 10
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
- Smith, C. Jeffrey; Katti, Kattesh V.; Volkert, Wynn A.
- Inorganic Chemistry, Vol. 36, Issue 18