Phthalocyanine tetrasulfonates bind to multiple sites on natively-folded prion protein

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DOIResolve DOI: http://doi.org/10.1016/j.bbapap.2012.03.011
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TypeArticle
Journal titleBiochimica et Biophysica Acta (BBA) - Proteins and Proteomics
ISSN1570-9639
Volume1824
Issue6
Pages826832; # of pages: 7
SubjectPrion protein; Phthalocyanine tetrasulfonate; Ligand binding; ITC; SPR; Fluorescence correlation spectroscopy
AbstractThe phthalocyanine tetrasulfonates (PcTS), a class of cyclic tetrapyrroles, bind to the mammalian prion protein, PrP. Remarkably, they can act as anti-scrapie agents to prevent the formation and spread of infectious, misfolded PrP. While the effects of phthalocyanines on the diseased state have been investigated, the interaction between PcTS and PrP has not yet been extensively characterized. Here we use multiple, complementary assays (surface plasmon resonance, isothermal titration calorimetry, fluorescence correlation spectroscopy, and tryptophan fluorescence quenching) to characterize the binding of PcTS to natively-folded hamster PrP(90–232), in order to determine binding constants, ligand stoichiometry, influence of buffer ionic strength, and the effects of chelated metal ions. We found that binding strength depends strongly on chelated metal ions, with Al³+ -PcTS binding the weakest and free-base PcTS the strongest of the three types tested (Al³+, Zn²+, and free-base). Buffer ionic strength also affected the binding, with Kd increasing along with salt concentration. The binding isotherms indicated the presence of at least two different binding sites with micromolar affinities and a total stoichiometry of ~ 4–5 PcTS molecules per PrP molecule.
Publication date
LanguageEnglish
AffiliationSecurity and Disruptive Technologies; National Research Council Canada
Peer reviewedYes
IdentifierS1570963912000581
NPARC number21268671
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Record identifier5fe0df17-1843-47b8-9166-98a67fb47f9f
Record created2013-11-07
Record modified2016-05-09
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