کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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30671 | 44495 | 2012 | 8 صفحه PDF | دانلود رایگان |
β-Lactoglobulin (β-LG) is a member of lipocalin superfamily of transporters for small hydrophobic molecules such as doxorubicin and its derivatives. We located the binding sites of doxorubicin (DOX) and N-(trifluoroacetyl) doxorubicin (FDOX) with β-lactoglobulin in aqueous solution at physiological conditions, using FTIR, CD and fluorescence spectroscopic methods as well as molecular modeling. Structural analysis showed that DOX and FDOX bind β-LG via both hydrophilic and hydrophobic contacts with overall binding constants of KDOX-β-LG = 1.0 (±0.4) × 104 M−1 and KFDOX-β-LG = 2.5 (±0.5) × 104 M−1 and the number of drug molecules bound per protein (n) 1.2 for DOX and 0.6 for FDOX. Molecular modeling showed the participation of several amino acids in the drug–protein complexes with the free binding energy of −8.12 kcal/mol for DOX-β-LG and −7.74 kcal/mol for FDOX-β-LG complexes. DOX and FDOX do not share similar binding sites with β-LG. Protein conformation showed minor alterations with reduction of β-sheet from 58% (free protein) to 57–51% in the drug-β-LG complexes. β-LG can transport doxorubicin and its derivative in vitro.
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► The binding sites of DOX and FDOX with milk beta-lactoglobulin are located.
► The drug–protein interaction is via hydrophobic and hydrophilic contacts.
► Several amino acids are involved in drug–protein bindings stabilized by H-bonding.
► DOX and FDOX do not share similar binding modes.
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 117, 5 December 2012, Pages 185–192