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Competition of drugs to serum albumin in combination therapy

✍ Scribed by Anna Sułkowska; Barbara Bojko; Joanna Równicka; Wiesław Sułkowski

Publisher
Wiley (John Wiley & Sons)
Year
2004
Tongue
English
Weight
264 KB
Volume
74
Category
Article
ISSN
0006-3525

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✦ Synopsis

Abstract

The mechanism of cooperative binding of both cytarabine and fluorouracil, used in combination therapy, to the transporting protein [bovine serum albumin (BSA)] has been investigated. Present study shows a strategy of estimating the kind of competition between these drugs with the use of uv and NMR spectroscopy. Two mechanisms of the competition to the transporting protein are proposed. For the quantitative investigations the effect of the protein on both the line width and chemical shifts of the NMR signals of the 5‐fluorouracil and cytarabine was analyzed. The π–π interaction between the pyrimidine ring of the drugs and the aromatic residues of the protein has been postulated. The binding site for both 5‐fluorouracil and cytarabine on BSA was found to be situated in the hydrophobic IIA subdomain. The competition of these two drugs and the removal of 5‐fluorouracil by cytarabine from the common binding site in serum albumin tertiary structure are observed. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004

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