Recent Findings in Human Serum Albumin Therapy Described by Researchers from Massachusetts Institute of Technology [Pt(IV) Prodrugs Designed to Bind Non-Covalently to Human Serum Albumin for Drug Delivery]
By a News Reporter-Staff News Editor at Biotech Week -- Investigators publish new report on Drugs and Therapies. According to news reporting originating in Cambridge, Massachusetts, by NewsRx journalists, research stated, "Albumin is the most abundant protein in human serum and drugs that are administered intravenously inevitably interact with it. We present here a series of platinum(IV) prodrugs designed specifically to enhance interaction with human serum albumin (HSA) for drug delivery."
The news reporters obtained a quote from the research from the Massachusetts Institute of Technology, "This goal is achieved by asymmetrically functionalizing the axial ligands of the prodrug so as to mimic the overall features of a fatty acid. Systematic variation of the length of the aliphatic tail tunes the cellular uptake and, consequently, the cytotoxicity of cis,cis,trans-[Pt(NH3)(2)Cl-2(O2CCH2CH2COOH)-(OCONHR)], 4, where R is a linear alkyl group. Investigation of an analogue bearing a fluorophore conjugated to the succinate ligand confirmed that these compounds are reduced by biological reductants with loss of the axial ligands. Intracellular release of cisplatin from 4 was further confirmed by observing the characteristic effects of cisplatin on the cell cycle and morphology following treatment with the prodrug. The most potent member of series 4, for which R is a hexadecyl chain, interacts with HSA in a 1:1 stoichiometry to form the platinum-protein complex 7. The interaction is non-covalent and extraction with octanol completely removes the prodrug from an aqueous solution of HSA. Construct 7 is robust and can be isolated following fast protein liquid chromatography. The nature of the tight interaction was investigated computationally, and these studies suggest that the prodrug is buried below the surface of the protein. Consequently, complexation to HSA is able to reduce the rate of reduction of the prodrug by ascorbate. The lead compound from series 4 also exhibited significant stability in whole human blood, attributed to its interaction with HSA."
According to the news reporters, the research concluded: "This favorable redox profile, in conjunction with the established nonimmunogenicity, biocompatibility, and enhanced tumor accumulation of HSA, produces a system that holds significant therapeutic potential."
For more information on this research see: Pt(IV) Prodrugs Designed to Bind Non-Covalently to Human Serum Albumin for Drug Delivery. Journal of the American Chemical Society, 2014;136(24):8790-8798. Journal of the American Chemical Society can be contacted at: Amer Chemical Soc, 1155 16TH St, NW, Washington, DC 20036, USA. (American Chemical Society - www.acs.org; Journal of the American Chemical Society - www.pubs.acs.org/journal/jacsat)
Our news correspondents report that additional information may be obtained by contacting Y.R. Zheng, MIT, Dept. of Chem, Cambridge, MA 02139, United States. Additional authors for this research include K. Suntharalingam, T.C. Johnstone, H. Yoo, W. Lin, J.G. Brooks and S.J. Lippard (see also Drugs and Therapies).
Keywords for this news article include: Cambridge, Massachusetts, United States, Blood Proteins, Drugs and Therapies, Human Serum Albumin, Acute-Phase Proteins, Drug Delivery Systems, North and Central America
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