Towards the functional high-resolution coordination chemistry of blood plasma human serum albumin

Al-Harthi, Samah; Lachowicz, Joanna Izabela; Nowakowski, Michał; Jaremko, Mariusz; Jaremko, Łukasz

doi:10.1016/j.jinorgbio.2019.110716

Cited by 108 publications

(90 citation statements)

References 179 publications

(317 reference statements)

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“…The values of geometric parameters for these adducts are reported in Table and their structures are in Figure S15 in the Supporting Information. These sites are reasonable candidates to represent those named B in the literature, with one His‐N plus O‐donors, which are the preferred by Co 2+ and Mn 2+ and are the second choice for Cd 2+ . On the basis of our results, it is important to note that B is not unique in the HSA d but comprises a number of similar binding sites that share the same chemical features.…”

Section: Resultsmentioning

confidence: 51%

“…The level of FAs influence the binding of zinc to albumin and it was proposed that they act as a regulatory mechanism of its concentration . Among the seven sites identified in HSA for medium‐ and long‐chain FAs (from C 10 to C 18 ) named FA1–FA7, FA2, FA4, and FA5 exhibit the highest affinity . The binding of FAs to the site FA2, located at the interface of the subdomains IA and IIA, causes their rotation, separating the coordinating amino acid of MBS, which becomes no longer available for Zn 2+ or, in general, for metal binding.…”

Section: Resultsmentioning

confidence: 99%

“…The distribution of FAs between the binding sites of HSA depends on their concentration in the blood and on chain length and unsaturation degree. In normal conditions, 1 mol of human serum albumin transports from 0.1 to 2 mol of FAs, and only at elevated FAs concentrations more than 2 mol are bound to HSA and all the sites are occupied . Taking into account that a significant fraction of FAs bind to FA4 and FA5 (i.e., those with the highest affinity together with FA2), MBS could remain unaltered and interact with the metal ions even in the presence of FAs.…”

Section: Resultsmentioning

confidence: 99%

“…The relationship between the binding of fatty acids (FAs) and some metal ions was suggested: it is proved that Zn 2+ coordination to the MBS can be hindered by the binding of FAs at their strongest site, FA2, causing a rotation of the subdomains where the MBS is located and separating the zinc amino acid donors. Such conformational changes can influence the binding of other metal ions and, therefore, the transport properties of albumin.…”

Section: Introductionmentioning

confidence: 99%

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Unveiling V^IVO²⁺ Binding Modes to Human Serum Albumins by an Integrated Spectroscopic–Computational Approach

Sciortino

Sanna

Lubinu

et al. 2020

Chemistry A European J

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Human serum albumin (HSA) is involved in the transport of metal ions and potential metallodrugs. Depending on the metal, several sites are available, among which are N‐terminal (NTS) and multi‐metal binding sites (MBS). Despite the large number of X‐ray determinations for albumins, only one structure with Zn2+ is available. In this work, the binding to HSA of the VIVO2+ ion was studied by an integrated approach based on spectroscopic and computational methods, which allowed the systems to be characterized even in the absence of X‐ray analysis. The behavior depends on the type of albumin, defatted (HSAd) or fatted (HSAf). With HSAd ‘primary’ and ‘secondary’ sites were revealed, NTS with (His3, His9, Asp13, Asp255) and MBS with (His67, His247, Asp249, Asn99 or H2O); with increasing the ratio VIVO2+/HSAd, ‘tertiary’ sites, with one His‐N and other donors (Asp/Glu‐O or carbonyl‐O) are populated. With HSAf, fatty acids (FAs) cause a rotation of the subdomains IA and IIA, which results in the formation of a dinuclear ferromagnetic adduct (VIVO)2D(HSAf) with a μ1,1‐Asp249 and the binding of His247, Glu100, Glu252, and His67 or Asn99. FAs hinder also the binding of VIVO2+ to the MBS.

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Section: Resultsmentioning

confidence: 51%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Unveiling V^IVO²⁺ Binding Modes to Human Serum Albumins by an Integrated Spectroscopic–Computational Approach

Sciortino

Sanna

Lubinu

et al. 2020

Chemistry A European J

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“…Starvation is able to induce stress by serum deprivation in vitro, 25 while albumin (the most abundant protein of serum) is the main carrier of essential metal ions and fatty acids for cells. 26 Butyrate, a short chain fatty acid produced by commensal bacteria of the human intestine, was already used to induce oxidative stress and apoptosis in CaCo2 cell cultures in Fauser et al 27 Moreover, it was reported that butyrate could act as an epigenetic "switch" of the immune system. 28 Butyric acid has been in fact associated with the ability to inhibit histone deacetylases (HDAC), and favors a state of acetylated histones in the cell.…”

Section: Resultsmentioning

confidence: 99%

Thymosin β4 cytoplasmic/nuclear translocation as a new marker of cellular stress. A Caco2 case study

et al. 2020

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Improving Metal Adsorption on Triethylenetetramine (TETA) Functionalized SBA‐15 Mesoporous Silica Using Potentiometry, EPR and ssNMR

Lachowicz

Emwas

Delpiano

et al. 2020

Adv Materials Inter

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Nanomaterials are receiving high attention in the treatment and diagnosis [3] of neurological disorders where the classical pharmacological approach is not effective due to low blood brain barrier (BBB) permeability. An effective drug delivery method is combining of drugs with nanocarriers, for example, polymeric micelles, liposomes, lipid, and polymeric nanoparticles (NPs), that have high BBB affinities. [4] Metal ion chelators, which are bound covalently to nanoparticles, can facilitate drug entry into the brain. [5] Desferrioxamine (Desferal) is an iron (Fe), aluminum (Al), copper (Cu), and zinc (Zn) chelator that showed a decrease of AD progression in clinical trials, [2,6] even if the low BBB permeability of DFO is still debatable. [7] DFO conjugated to polystyrene NPs of 240 nm and examined in human cortical neurons in vitro prevented Aβ peptide aggregation, [8] the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. [9] Nevertheless, low bioavailability and high toxicity restrict the use of metal chelators in humans. Functional nanoparticles are characterized by multiple incorporation of positron emitting radionuclides and signal enhancement in positron emission tomography (PET). [10] It has been Nanomaterials have received growing attention in the treatment and diagnosis of neurological disorders because the low blood brain barrier permeability hinders the classical pharmacological approach. Metal ion chelators combined with nanoparticles prove effective in the treatment of neurodegeneration and are under extensive studies. Most chelating agents and metallodrugs compete with endogenous molecules for metal coordination, and do not reach the active site. Determining the competition between metallodrugs and endogenous molecules requires knowing the stability constants of formed metal complexes. In this study, for the first time, potentiometric titrations are used to determine metal complex formation constants, and to quantify ligand content in functionalized materials. This new potentiometric approach allows physico-chemical characterization of mesoporous functionalized materials and their metal adsorption capacity in water solution. The potentiometric results are compared with isotherm models obtained by spectroscopic measurements and yield rewarding data fitting. The potentiometric method described here can be extended to different types of nanostructured materials carrying surface ionizable groups.

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Towards the functional high-resolution coordination chemistry of blood plasma human serum albumin

Cited by 108 publications

References 179 publications

Unveiling V^IVO²⁺ Binding Modes to Human Serum Albumins by an Integrated Spectroscopic–Computational Approach

Unveiling V^IVO²⁺ Binding Modes to Human Serum Albumins by an Integrated Spectroscopic–Computational Approach

Thymosin β4 cytoplasmic/nuclear translocation as a new marker of cellular stress. A Caco2 case study

Improving Metal Adsorption on Triethylenetetramine (TETA) Functionalized SBA‐15 Mesoporous Silica Using Potentiometry, EPR and ssNMR

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Towards the functional high-resolution coordination chemistry of blood plasma human serum albumin

Cited by 108 publications

References 179 publications

Unveiling VIVO2+ Binding Modes to Human Serum Albumins by an Integrated Spectroscopic–Computational Approach

Unveiling VIVO2+ Binding Modes to Human Serum Albumins by an Integrated Spectroscopic–Computational Approach

Thymosin β4 cytoplasmic/nuclear translocation as a new marker of cellular stress. A Caco2 case study

Improving Metal Adsorption on Triethylenetetramine (TETA) Functionalized SBA‐15 Mesoporous Silica Using Potentiometry, EPR and ssNMR

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Unveiling V^IVO²⁺ Binding Modes to Human Serum Albumins by an Integrated Spectroscopic–Computational Approach

Unveiling V^IVO²⁺ Binding Modes to Human Serum Albumins by an Integrated Spectroscopic–Computational Approach