Binding interactions and conformational changes induced by sulfonated aluminum phthalocyanines in human serum albumin

被引:29
作者
Gantchev, TG [1 ]
Ouellet, R [1 ]
van Lier, JE [1 ]
机构
[1] Univ Sherbrooke, Fac Med, Dept Med Nucl & Radiobiol, Sherbrooke, PQ J1H 5N4, Canada
基金
英国医学研究理事会;
关键词
serum albumin (human); metallo-phthalocyanine(s); photodynamic therapy (PDT); binding interactions (ligand); protein conformational dynamics; ESR spectroscopy;
D O I
10.1006/abbi.1999.1174
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Phthalocyanines (Pc), which are extensively studied as tumor localizing photosensitizers for photodynamic therapy, are transported by the blood circulatory system to target tissues, finding 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 SO3- groups on adjacent iso-indole rings exhibit a high affinity binding site constant of K similar to 3-4 x 10(7) M-1, while Pc with two or three adjacent SO3- groups show binding for this high affinity site that is no longer independent, but cooperative (alpha = 2), with K similar to 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 (tau(c) 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. (C) 1999 Academic Press.
引用
收藏
页码:21 / 30
页数:10
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