The Distribution of Fatty Acids Reveals the Functional Structure of Human Serum Albumin

Junk, Matthias J. N.; Spiess, Hans Wolfgang; Hinderberger, Dariush

doi:10.1002/anie.201003495

Cited by 67 publications

(164 citation statements)

References 37 publications

Supporting

Mentioning

143

Contrasting

Order By: Relevance

“…indicating that all six equivalents of 16DS can bind to HSA, as reported previously [20]. The situation is different in the case of the SLFA-to-HSA molar ratio 8:1 where the signal from the unbound SLFA can be clearly observed on the high-field side (marked with an arrow in Fig.…”

Section: Binding Of Complex 5 In Presence Of Long-chain Fatty Acids: supporting

confidence: 74%

“…This is an efficient and widely used method for studying the binding of FAs to albumin [18][19][20][21][22][23], as well as the competition between FAs and other compounds although its application for metal complexes is fairly rare in the literature [24]. Furthermore, displacement experiments with wellestablished markers for sites I and II, namely warfarin (WF) and dansylglycine (DG), respectively, were also performed and the data is discussed.…”

Section: Interaction Of Anticancer Metallodrugs With Proteins Is Of Cmentioning

confidence: 99%

“…Since complexes 1-5 showed similar binding affinities for HSA (Table 1), the binding of complex 5 was further studied in the presence of a stearic FA, labeled with an aminoxyl radical at position C-16 (16-doxyl stearic acid, 16DS), a spin label that has been used in many previous studies [18][19][20]22,23]. It is important to note that the binding of FAs to HSA is not perturbed by spin labeling of FAs [20], hence the EPR spin labeling technique can provide reliable information about the amount of the FAs bound to HSA.…”

Section: Binding Of Complex 5 In Presence Of Long-chain Fatty Acids: mentioning

confidence: 99%

“…It is important to note that the binding of FAs to HSA is not perturbed by spin labeling of FAs [20], hence the EPR spin labeling technique can provide reliable information about the amount of the FAs bound to HSA.…”

Section: Binding Of Complex 5 In Presence Of Long-chain Fatty Acids: mentioning

confidence: 99%

See 3 more Smart Citations

Investigation of the binding of cis/trans-[MCl4(1H-indazole)(NO)]− (M = Ru, Os) complexes to human serum albumin

Dömötör

Rathgeb

Kuhn

et al. 2016

Journal of Inorganic Biochemistry

View full text Add to dashboard Cite

Overall binding affinity of sodium or indazolium cis/trans-[MCl 4 (1H-indazole)(NO)] (M = Ru,Os) complexes towards human serum albumin (HSA) and high molecular mass components of the blood serum was monitored by ultrafiltration. HSA was found to be mainly responsible for the binding of the studied ruthenium and osmium complexes. In other words, this protein can provide a depot for the compounds and can affect their biodistribution and transport processes. In order to elucidate the HSA binding sites tryptophan fluorescence quenching studies and displacement reactions with the established site markers warfarin and dansylglycine were performed. Conditional stability constants for the binding to sites I and II on HSA were computed showing that the studied ruthenium and osmium complexes are able to bind into both sites with moderately strong affinity (logK' = 4.4-5.1). Site I is slightly more favored over site II for all complexes. No significant differences in the HSA binding properties were found for these metal complexes demonstrating negligible influence of the type of counter ion (sodium vs. indazolium), the metal ion center identity (Ru vs. Os) or the position of the nitrosyl group on the binding 2 event. Electron paramagnetic resonance spin labeling of HSA revealed that indazolium trans-[RuCl 4 (1H-indazole)(NO)] and long-chain fatty acids show competitive binding to HSA.Moreover, this complex has a higher affinity for site I, but when present in excess, it is able to bind to site II as well, and displace fatty acids.

show abstract

Section: Binding Of Complex 5 In Presence Of Long-chain Fatty Acids: supporting

confidence: 74%

Section: Interaction Of Anticancer Metallodrugs With Proteins Is Of Cmentioning

confidence: 99%

Section: Binding Of Complex 5 In Presence Of Long-chain Fatty Acids: mentioning

confidence: 99%

Section: Binding Of Complex 5 In Presence Of Long-chain Fatty Acids: mentioning

confidence: 99%

See 2 more Smart Citations

Investigation of the binding of cis/trans-[MCl4(1H-indazole)(NO)]− (M = Ru, Os) complexes to human serum albumin

Dömötör

Rathgeb

Kuhn

et al. 2016

Journal of Inorganic Biochemistry

View full text Add to dashboard Cite

show abstract

“…The Jeschke distribution of up to six fatty acid ligands was studied by adding 5-doxyl-or 16-doxyl-stearic acid to the apoprotein and measuring the distance distributions between the labels (124). Experimental data revealed a much more symmetric distribution of the ligands than had been previously observed in a crystal structure of the HSA complex with fatty acids, in particular for the hydrophobic chain end at position 16.…”

Section: Ligand Bindingmentioning

confidence: 93%

DEER Distance Measurements on Proteins

Jeschke

2012

Annu. Rev. Phys. Chem.

921

1,073

View full text Add to dashboard Cite

Distance distributions between paramagnetic centers in the range from 1.8 to 6 nm in membrane proteins and up to 10 nm in deuterated soluble proteins can be measured by the DEER technique. The number of paramagnetic centers and their relative orientation can be characterized. DEER does not require crystallization and is not limited with respect to the size of the protein or protein complex. Diamagnetic proteins are accessible by site-directed spin labeling. To characterize structure or structural changes, the experimental protocols were optimized and techniques for artifact suppression were introduced. Data analysis programs were developed and it was realized that interpretation of the distance distributions must take into account the conformational distribution of spin labels. First methods have appeared for deriving structural models from a small number of distance constraints. The current scope and limitations of the technique are illustrated.

show abstract

A Polyphenylene Dendrimer Drug Transporter with Precisely Positioned Amphiphilic Surface Patches

Stangenberg

Hedrich

et al. 2014

Adv Healthcare Materials

Self Cite

View full text Add to dashboard Cite

The design and synthesis of a polyphenylene dendrimer (PPD 3) with discrete binding sites for lipophilic guest molecules and characteristic surface patterns is presented. Its semi-rigidity in combination with a precise positioning of hydrophilic and hydrophobic groups at the periphery yields a refined architecture with lipophilic binding pockets that accommodate defined numbers of biologically relevant guest molecules such as fatty acids or the drug doxorubicin. The size, architecture, and surface textures allow to even penetrate brain endothelial cells that are a major component of the extremely tight blood-brain barrier. In addition, low to no toxicity is observed in in vivo studies using zebrafish embryos. The unique PPD scaffold allows the precise placement of functional groups in a given environment and offers a universal platform for designing drug transporters that closely mimic many features of proteins.

show abstract

The Distribution of Fatty Acids Reveals the Functional Structure of Human Serum Albumin

Cited by 67 publications

References 37 publications

Investigation of the binding of cis/trans-[MCl4(1H-indazole)(NO)]− (M = Ru, Os) complexes to human serum albumin

Investigation of the binding of cis/trans-[MCl4(1H-indazole)(NO)]− (M = Ru, Os) complexes to human serum albumin

DEER Distance Measurements on Proteins

A Polyphenylene Dendrimer Drug Transporter with Precisely Positioned Amphiphilic Surface Patches

Contact Info

Product

Resources

About