β-Cyclodextrin Reverses Binding of Perfluorooctanoic Acid to Human Serum Albumin

Abstract

Perfluorooctanoic acid (PFOA), a persistent organic pollutant known to cause adverse health effects, strongly binds to human serum albumin (HSA). β-Cyclodextrin (β-CD), a nontoxic cyclic sugar, strongly complexes PFOA in a host-guest complex and has been proposed for environmental remediation of PFOA. The interactions between HSA, PFOA, and β-CD were investigated in order to determine if β-CD can reverse the binding of PFOA to HSA, with potential therapeutic applications toward exposure to PFOA. F Nuclear magnetic resonance (NMR), circular dichroism, and fluorescence spectroscopies were used to study these interactions. Multiple PFOA binding sites to HSA, one with strong affinity and others with low affinity, are evident from changes in the fluorescence emission spectra of HSA and the fluorescence lifetimes of the single Trp residue in HSA with increasing PFOA concentration. Structural changes in the protein are also evident from changes in the circular dichroism spectra of HSA upon titration of PFOA. Addition of β-CD to PFOA and HSA reversed these changes, indicating that formation of the β-CD:PFOA host-guest complex is favored even in the presence of HSA. Equimolar β-CD to PFOA (1:1 β-CD:PFOA ratio) causes dissociation of the weakly bound PFOA from HSA, whereas excess β-CD relative to PFOA (5:1 β-CD:PFOA ratio) leads to the complete disassociation of the strongly bound PFOA molecule from HSA. TheF NMR studies further suggest that the 2:1 β-CD:PFOA complex inhibits PFOA binding to HSA. These data demonstrate that β-CD has potential to be used in therapeutic applications for PFOA in human blood.

Comprehensive Insights into the Interactions of Two Emerging Bromophenolic DBPs with Human Serum Albumin by Multispectroscopy and Molecular Docking

“…To detect the effects of the two DBPs on the secondary structure of HSA, CD spectra of HSA with various amounts of the DBPs were measured (Figure c,d). In general, two negative bands at around 208 and 222 nm represent the characteristic absorption of the α-helix structure in HSA . As can be seen from the graph, the intensities of the two negative bands changed evidently upon the addition of 4-BrPh/2,4-DiBrPh, implying the alterations of the secondary structure of HSA.…”

“…In general, two negative bands at around 208 and 222 nm represent the characteristic absorption of the α-helix structure in HSA. 49 As can be seen from the graph, the intensities of the two negative bands changed evidently upon the addition of 4-BrPh/2,4-DiBrPh, implying the alterations of the secondary structure of HSA. The CDPro software was adopted to analyze the CD spectra and to calculate the fractions of α-helix, β-sheet, β-turn, and random coil by using SELCON3 method.…”

Nanopore sensing of γ‐cyclodextrin induced host‐guest interaction to reverse the binding of perfluorooctanoic acid to human serum albumin

“…Previous studies have probed β‐CD inhibition and reverse of HSA‐PFOA binding using NMR, circular dichroism, and fluorescence spectroscopies [17]. In this study, we investigated γ‐CD mediated inhibition and reverse of HSA‐PFOA binding with nanopore sensing and confirmed with NMR.…”

“…Upon introduction of samples to the cis side, all samples enter the nanochannel through the head of α-HL, causing current blockade events which are then recorded and analyzed (Figure 1) This result indicates that the introduction of HSA has less effect on the interaction between γ-CD and the nanopore, which can be attributed to the mismatched sizes of HSA (∼80 Å) [28] and α-HL (∼13 Å) [29] and the weak interaction between HSA and γ-CD with a cavity diameter of ∼ 8.6 Å. [2,30] When PFOA (13 Å × 6.5 Å × 6.5 Å) [31] was introduced, Previous studies have probed β-CD inhibition and reverse of HSA-PFOA binding using NMR, circular dichroism, and fluorescence spec-troscopies [17]. In this study, we investigated γ-CD mediated inhibition and reverse of HSA-PFOA binding with nanopore sensing and confirmed with NMR.…”

“…For example, β-CD can encapsulate PFOA strongly in a host-guest complex without being disturbed by changes in solution [16]. The competition behavior for the complexation of PFOA between HSA and β-CD have been probed employing 19F nuclear magnetic resonance (NMR), circular dichroism, and fluorescence spectroscopies [17], which have been extensively exploited and are routine methods for investigating and determining the interaction between different molecules.…”