Binding interactions and conformational changes induced by sulfonated aluminum phthalocyanines in human serum albumin.
Phthalocyanines (Pc), which are extensively studied as tumor localizing photosensitizers for photodynamic therapy, are transported by the blood circulatory system to target tissues. Binding interactions between human serum albumin and differently sulfonated aluminum phthalocyanines (AlPcSn; n = 1-4) were studied using optical and ESR spectroscopy. AlPcSn (n = 1-3) occupy one strong binding site and eight weaker sites. The high affinity binding site interactions differ with respect to the degree of sulfonation and isomeric composition of the Pc. Phthalocyanines without SO-3 groups on adjacent iso-indole rings exhibit a high affinity binding site constant of K approximately 3-4 x 10(7) M-1, while Pc with two or three adjacent SO-3 groups show binding for this high affinity site that is no longer independent, but cooperative (alpha = 2), with K approximately 2-6 x 10(6) M-1. Binding isotherms for AlPcS4 and its close analog, tempoyl spin-labeled SL-AlPcS3, do not approach saturation at high ligand concentrations. Competition analyses between AlPcSn and spin-labeled fatty acids (5- and 16-doxyl stearate isomers) reveal that all compounds participate in cooperative (allosteric) interactions with the high affinity binding site of 16-DS, while extruding 5-DS isomer from certain sites and increasing the binding affinity for the remaining. Protein conformational dynamics was studied by ESR spectroscopy using covalent (alkylation of Cys34 residue) and noncovalent spin labeling (employing SL-AlPcS3). Phthalocyanines perturb conformational dynamics parameters (tauc and S) depending on the degree of sulfonation and isomeric composition corresponding to the type of sites, i.e., independent or cooperative, occupied on the HSA molecule.
Gantchev
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TG
Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, J1H 5N4, Canada. gantchev@courrier.usherb.ca
Ouellet
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R
van Lier
J E
JE
D000494:Allosteric Regulation; D000535:Aluminum / Q000494:pharmacology*; D001190:Arylsulfonates / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D007211:Indoles / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000494:pharmacology*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011487:Protein Conformation; D012709:Serum Albumin / Q000737:chemistry* / Q000187:drug effects
D001190:Arylsulfonates; D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D012709:Serum Albumin; C060570:aluminum phthalocyanine; D000535:Aluminum