Formation Of Conjugates Research Articles

The septin cytoskeleton regulates natural killer cell lytic granule release.

Natural killer (NK) cell-mediated killing involves the membrane fusion of preformed lytic granules. While the roles of actin and microtubules are well accepted during this process, the function of septins, another cytoskeletal component that associates with actin and microtubules, has not been investigated. Here we show that genetic depletion or pharmacologic stabilization of the septin cytoskeleton significantly inhibited NK cell cytotoxicity. Although the stabilization of septin filaments impaired conjugate formation, depletion of septin proteins had no impact on conjugate formation, lytic granule convergence, or MTOC polarization to the cytotoxic synapse (CS). Interestingly, septins copurify and accumulate near the polarized lytic granules at the CS, where they regulate lytic granule release. Mechanistically, we find that septin 7 interacts with the SNARE protein syntaxin 11 and facilitates its interaction with syntaxin binding protein 2 to promote lytic granule fusion. Altogether, our data identify a critical role for septins in regulating the release of lytic granule contents during NK cell-mediated killing.

Mechanisms Underlying Development of Taurine-Deficient Cardiomyopathy

Taurine is a ubiquitous β-amino acid that plays an essential role in ensuring normal mitochondrial and myocardial function. In the mitochondria, taurine reacts with a tRNA forming a 5-taurinomethyluridine conjugate that primarily regulates the biosynthesis of the mitochondria encoded protein, ND6, which serves as a subunit of complex I of the respiratory chain. Impaired formation of the taurine conjugate reduces activity of complex I and plays a central role in the pathophysiology of the mitochondrial disease MELAS (myopathy, encephalopathy, lactic acidosis and stroke-like episodes). The restoration of mitochondrial levels of the taurine conjugate enhances electron flux through the respiratory chain, thereby preventing at least some of the symptoms of MELAS. Taurine therapy also diminishes the severity of congestive heart failure, an observation that led to its approval for the treatment of congestive heart failure in Japan. The review article discusses the role of defective calcium handling, reduced ATP generation, enhanced oxidative stress and apoptosis in the development of taurine-deficient cardiomyopathy. Some patients suffering from congestive heart failure are taurine-deficient, an observation supporting the hypothesis that low taurine levels contribute to the severity of heart failure. Thus, mishandling of taurine leads to mitochondrial dysfunction, which is involved in the development of both MELAS and congestive heart failure.

γ9δ2T cell diversity and the receptor interface with tumor cells.

γ9δ2T cells play a major role in cancer immune surveillance, yet the clinical translation of their in vitro promise remains challenging. To address limitations of previous clinical attempts using expanded γ9δ2T cells, we explored the clonal diversity of γ9δ2T cell repertoires and characterized their target. We demonstrated that only a fraction of expanded γ9δ2T cells was active against cancer cells and that activity of the parental clone, or functional avidity of selected γ9δ2 T cell receptors (γ9δ2TCRs), was not associated with clonal frequency. Furthermore, we analyzed the target-receptor interface and provided a 2-receptor, 3-ligand model. We found that activation was initiated by binding of the γ9δ2TCR to BTN2A1 through the regions between CDR2 and CDR3 of the TCR γ chain and modulated by the affinity of the CDR3 region of the TCRδ chain, which was phosphoantigen independent (pAg independent) and did not depend on CD277. CD277 was secondary, serving as a mandatory coactivating ligand. We found that binding of CD277 to its putative ligand did not depend on the presence of γ9δ2TCR, did depend on usage of the intracellular CD277, created pAg-dependent proximity to BTN2A1, enhanced cell-cell conjugate formation, and stabilized the immunological synapse (IS). This process critically depended on the affinity of the γ9δ2TCR and required membrane flexibility of the γ9δ2TCR and CD277, facilitating their polarization and high-density recruitment during IS formation.

Temperature-induced interaction with carboxymethyl cellulose affected the rheological properties and structure of wheat gluten

Carboxymethyl cellulose (CMC) is commonly used as a hydrocolloid in wheat breadmaking to improve the technological and sensory quality. The experiment focuses on effects of the interactions between different levels (0.5% and 1.0% gluten basis) of CMC and gluten on the structure and rheological properties during heating process using fourier transform infrared spectroscopy (FTIR), dynamic oscillatory rheology, confocal laser scanning microscopy (CLSM) and isothermal titration calorimetry (ITC). The results showed that the presence of 0.5% CMC could reduce the aggregation extent and reinforce the cross-linked network through the formation of protein-polysaccharide conjugates during heating process, which could increase the viscoelastic properties of gluten. Structural studies showed that 0.5% CMC-gluten mixtures have higher contents of β-structures (46.12%) compared with control (36.81%). On the contrary, more open and heterogeneous microstructures of gluten were observed with 1.0% CMC, which led to the decreased viscoelastic properties. Structural studies showed there was a decrease in antiparallel β-sheets (6.99%) and β-turns (9.34%) accompanied an increase by intermolecular β-sheets (9.75%) and α-helices (9.32%) for the 1.0% CMC-gluten mixture during the heating process. The analyses of ITC showed that the protein-polysaccharide conjugates formed through Maillard-type reaction during heating.

Conjugation of citrate capped gold nanoparticles with gabapentin to use as biosensor

Identification of biomolecules in body fluid or biological tissue is important for proper diagnosis and treatment. Biosensors can be used to detect the bio-molecules in the body. These also have wide applicability in the field of diagnosis of different neural disorders. Antibody and enzyme- based biosensors are already used for sensing and diagnosis. But the neurotransmitter based biosensors are not available for identification of specific brain areas till date. In the field of the biosensor, gold nanoparticle attracts much interest due to its lesser toxicity and good surface Plasmon characteristics. Present research work has been designed to conjugate gold nanoparticles with neurotransmitter derivative, the gabapentin. Citrate stabilized gold nanoparticles were conjugated with gabapentin and the characteristics of the conjugate were studied. UV–visible spectrum clearly showed the formation of the conjugate. The stability study of the conjugate showed that the conjugate was stable for a prolonged period. PL study of the conjugate indicated that the conjugate had fluorescence characteristics. Zeta potential study of the gabapentin and gold nanoparticles showed the possibility of the conjugate formation. The gold nanoparticles may conjugate with the gabapentin due to electrostatic attraction between them. It was observed that conjugation of citrate capped gold nanoparticles with gabapentin showed interaction with brain cell as demonstrated by fluorescence microscopy. Hence, citrate capped gold nanoparticles-gabapentin conjugate can be used as base compound for development of neurotransmitter based biosensor.

Hydroxypropylcellulose-flurbiprofen conjugates: design, characterization, anti-inflammatory activity and enhanced bioavailability

Herein, we report novel macromolecular prodrugs (MPDs) of flurbiprofen (FLB) onto a cellulose ether, hydroxypropylcellulose (HPC). The FLB was activated with a powerful acylation reagent carbonyldiimadazole (CDI) in N,N′ dimethylacetamide (DMAc) solvent at room temperature. Imidazolide of FLB generated in situ reacts at 80 °C for 24 h with pre-dissolved HPC to prepare HPC-FLB conjugates. The resultant MPDs of FLB showed moderate to high degree of substitution (DS: 0.35–1.3) with good yield (70–82%). Structures were thoroughly characterized using FTIR, UV and NMR spectroscopic analyses. The pharmacokinetic studies showed that the t1/2 and tmax values of FLB from HPC-FLB conjugate were increased substantially as compare to standard FLB indicates enhanced bioavailability of drug after conjugate formation. Remarked anti-inflammatory activity of the HPC-FLB conjugate was also observed.

Dietary Genistein Reduces Methylglyoxal and Advanced Glycation End Product Accumulation in Obese Mice Treated with High-Fat Diet.

Our previous study has found that dietary genistein could ameliorate high-fat diet (HFD)-induced obesity and especially lower methylglyoxal (MGO) and advanced glycation end product (AGE) accumulation in healthy mice exposed to genistein and HFD. However, it is still unclear whether dietary genistein intervention has a similar beneficial effect in obese mice. In this study, the mice were induced with obesity after being fed a HFD for nine weeks before being administered with two doses of genistein, 0.1% (G 0.1) and 0.2% (G 0.2), in the HFD for additional 19 weeks. After 19 week treatment, genistein supplementation reduced body and liver weights, plasma and liver MGO levels, and kidney AGE levels in mice. Mechanistically, genistein upregulated the expressions of glyoxalase I and II and aldose reductase to detoxify MGO, and genistein and its microbial metabolites, dihydrogenistein and 6'-hydroxy-O-demethylangolensin, were able to trap endogenous MGO via formation of MGO conjugates. Taken together, our results provide novel insights into the antiobesity and antiglycation roles of dietary genistein in obese subjects.

Whey protein isolate-low acyl gellan gum Maillard-based conjugates with tailored technological functionality and antioxidant activity

Whey proteins are usually sensitive to ionic strength, pH change, and heat treatment, which may affect their functional properties. Maillard conjugation could be a facile approach to improve whey protein functionality. In this study, whey protein isolate (WPI; 0.6%, w/v) was conjugated to low acyl gellan gum (0.1, 0.2, and 0.3%, w/v) through the Maillard reaction at 90 °C for 90 min. The conjugate formation was confirmed by pH decrement, glycation degree (up to 9.44%), browning index, sodium dodecyl sulphate-polyacrylamide gel electrophoresis, and Fourier transform infrared spectroscopy. The surface hydrophobicity of WPI increased up to 2-fold upon conjugation, which led to a solubility decrease. However, the conjugated WPI had an improved interfacial activity, emulsifying activity (∼6%), foaming capacity (up to 63.64%), thickening ability (up to 24.67-fold), reducing power (up to 28.86-fold), and iron chelating activity (up to 3.31-fold). These findings may widen the industrial application of whey proteins.

Identification of Novel Low-Weight Sulfhydryl Conjugates of Oxidized 5-O- and 6-O-Substituted Betanidin Pigments.

The formation of conjugates of oxidized betacyanin pigments with selected low-weight sulfhydryl scavengers was studied. Short-lived quinonoids, quinone methides, and aminochromes derived from oxidized betacyanins are able to form adducts with different efficiencies. In this report, mass spectrometric and NMR identifications of CS-linked conjugates of cysteine, cysteamine, N-acetylcysteine, and dl-dithiolthreitol with quinonoid forms generated through oxidation of betanidin, betanin, and gomphrenin is presented. An adduct that formed between cysteine and quinonoid generated from betanin by its oxidation and decarboxylation (2-decarboxy-xanbetanin) was detected and reported for the first time. The most stable gomphrenin CS-conjugate, N-acetylcysteinylated gomphrenin, was isolated by semipreparative chromatography and its structure was established by NMR analysis. This enabled to confirm the conjugation position at carbon C-4 and to indicate the presence of a dopachromic intermediate during oxidation of gomphrenin. Conjugation of betacyanins with thiol-bearing moieties may generate new molecules with modified chemical and biological properties. Obtained results confirm that gomphrenin is capable of forming CS-conjugates with higher efficiency than betanin.

Conjugation of soy protein isolate (SPI) with pectin by ultrasound treatment

The Maillard reaction in the aqueous system with and without ultrasound treatment was used to prepare conjugates between soy protein isolate (SPI) and citrus pectin (CP)/apple pectin (AP). Ultrasound treatment at a power of 450 W and a temperature of 70 °C significantly accelerated the conjugation processes between SPI and pectin samples and led to much greater grafting extents compared to the traditional wet heating. A higher degree of graft of the SPI-CP conjugates was achieved at a shorter ultrasound duration compared to the SPI-AP conjugates, possibly attributed to the larger molecular weight and the more flexible structure of AP. SDS-PAGE analysis confirmed the formation of SPI-pectin conjugates. Analysis of the protein secondary and tertiary structures suggested that the attachment of CP or AP changed the spatial conformation of SPI and led to a looser protein structure. In addition to the grafting process, ultrasound was also observed to play a marked role in unfolding the SPI resulting in more favorable structures for the Maillard reaction. Furthermore, the application of ultrasound to the conjugation process significantly increased the surface hydrophobicity and emulsifying properties of both conjugates, indicating that ultrasound can be a desirable method for protein-polysaccharide conjugation.

Enhanced antimicrobial efficacy of biosynthesized silver nanoparticle based antibiotic conjugates

Multidrug resistant and biofilm forming microorganisms generate much concern to the healthcare sector. Hence alternative strategies for their control by exploring the nanomedicinal advantages of silver nanoparticles (AgNPs) are highly significant. Large surface area to volume ratio and the multi-targeted antimicrobial effects of AgNPs are highly remarkable. In the study, AgNPs synthesized by a Bacillus sp. SJ14 were studied for its antibacterial activity in combination with ciprofloxacin, methicillin, gentamicin and rifampicin. The AgNP based antibiotic conjugate formation was analyzed by UV–visible and FT-IR spectroscopy. The prepared conjugates were tested against multidrug resistant and biofilm forming coagulase-negative Staphylococcus epidermidis and Staphylococcus haemolyticus strains of clinical origin. The conjugation formation was found to decrease the minimum inhibitory concentration (MIC) of antibiotics significantly. The MIC of most of the conjugates showed reduction, notably the MIC of methicillin was reduced from 250 µg/mL to 7.8 µg/mL against S. epidermidis. By fractional inhibitory concentration (FIC) analysis, synergistic action of nanoparticles and antibiotics could be confirmed in all the cases except rifampicin. Hence the nanomedicine studied can have significant therapeutic application to manage organisms associated with device-related infections.

Formation of glutathione patulin conjugates associated with yeast fermentation contributes to patulin reduction

Patulin (PAT) is a fungal secondary metabolite which is mainly detected in rotten apples, and possesses serious risks to human health. Saccharomyces cerevisiae has become a promising biological control candidate due to its ability to degrade PAT. However, the degradation mechanism remains elusive. In this study, the degradation system and potential other metabolisms of PAT by S. cerevisiae were investigated. After a 96 h fermentation, 5.0 mg/L of PAT was completely metabolized by S. cerevisiae. Among the mixture of metabolites, ascladiol was identified but only accounted for 3.3% of the initial PAT. Yeast cell lysates, attained from a 96 h culture, altered 10 mg/L of PAT within 8 h. As this activity was reduced by heat treatment, it indicated that soluble intracellular enzymes were key components in PAT transformation. In addition, these effective intracellular enzymes were obtained in PAT-treated yeast cells instead of the untreated cells, indicating the activity was induced by PAT. LC-MS/MS revealed a drastic decrease of glutathione (GSH) in cell lysate upon addition of PAT. Several glutathione-patulin (GSH-PAT) conjugates (mainly c-GSH-PAT and l-GSH-PAT) were later identified. The conjugation of GSH and PAT plays an important role in PAT reduction by yeast cell lysate, even after enzymes in the lysate have been heat inactivated. Therefore, the PAT reduction by S. cerevisiae was a consequence of PAT-induced intracellular enzymes and GSH-mediated conjugation.

Enhanced biological activity of polyphenols on conjugation with gellan gum

The gellan gum was coupled with hydrophobic polyphenols, curcumin and naringenin using dicyclohexylcarbodiimide and dimethylaminopyridine reaction. The formation of conjugates was ascertained by spectral, thermal, X-ray diffraction, and scanning electron microscopic studies. In silico simulations validated the successful interaction between polysaccharide and polyphenols. The conjugates self-assemble in aqueous solution was confirmed by fluorescence spectroscopy and dynamic light scattering. Further, evaluation unveiled significantly improved radical scavenging and antibacterial activity of conjugates over pristine polyphenols. The conjugates revealed higher anti-cancer activity against human ovarian carcinoma cell lines. In conclusion, polyphenol conjugates showed improved therapeutic efficiency and delivery on conjugation with gum.

Chemically Induced Vinylphosphonothiolate Electrophiles for Thiol-Thiol Bioconjugations.

Herein we introduce vinylphosphonothiolates as a new class of cysteine-selective electrophiles for protein labeling and the formation of stable protein-protein conjugates. We developed a straightforward synthetic route to convert nucleophilic thiols into electrophilic, thiol-selective vinylphosphonothiolates: In this protocol, intermediately formed disulfides can be chemoselectively substituted with vinylphosphonites under acidic conditions to yield the desired vinylphosphonothiolates. Notably, this reaction sequence enables the installation of vinylphosphonothiolate electrophiles directly on cysteine side chains within peptides and proteins. In addition to labeling the monoclonal antibody trastuzumab with excellent cysteine-selectivity, we applied our protocol for the site-specific conjugation of two proteins with unique cysteine residues yielding a nonhydrolyzable phosphonothiolate-linked diubiquitin and an ubiquitin-α-synuclein conjugate. The latter was recognized as a substrate in a subsequent enzymatic ubiquitination reaction.

Pyrocinchonimides Conjugate to Amine Groups on Proteins via Imide Transfer.

Advances in bioconjugation, the ability to link biomolecules to each other, small molecules, surfaces, and more, can spur the development of advanced materials and therapeutics. We have discovered that pyrocinchonimide, the dimethylated analogue of maleimide, undergoes a surprising transformation with biomolecules. The reaction targets amines and involves an imide transfer, which has not been previously reported for bioconjugation purposes. Despite their similarity to maleimides, pyrocinchonimides do not react with free thiols. Though both lysine residues and the N-termini of proteins can receive the transferred imide, the reaction also exhibits a marked preference for certain amines that cannot solely be ascribed to solvent accessibility. This property is peculiar among amine-targeting reactions and can reduce combinatorial diversity when many available reactive amines are available, such as in the formation of antibody-drug conjugates. Unlike amides, the modification undergoes very slow reversion under high pH conditions. The reaction offers a thermodynamically controlled route to single or multiple modifications of proteins for a wide range of applications.

Fluorophore-Assisted Click Chemistry through Copper(I) Complexation.

The copper-catalyzed alkyne-azide cycloaddition (CuAAC) is one of the most powerful chemical strategies for selective fluorescent labeling of biomolecules in in vitro or biological systems. In order to accelerate the ligation process and ensure efficient formation of conjugates under diluted conditions, external copper(I) ligands or sophisticated copper(I)-chelating azides are used. This latter strategy, however, increases the bulkiness of the triazole linkage, thus perturbing the biological function or dynamic behavior of the conjugates. In a proof-of-concept study, we investigated the use of an extremely compact fluorophore-based copper(I) chelating azide in order to accelerate the CuAAC with concomitant fluorescence labeling; in our strategy, the fluorophore is able to complex copper(I) species while retaining its photophysical properties. It is believed that this unprecedented approach which was applied for the labeling of a short peptide molecule and the fluorescent labeling of live cells, could be extended to other families of nitrogen-based fluorophores in order to tune both the reaction rate and photophysical characteristics.

Effect of different carbohydrates on the functional properties of black rice glutelin (BRG) modified by the maillard reaction

The objective of this study was to investigate the effects of the glycosylation of BRG on its structures and functional properties. The glycosylation of BRG was achieved via Maillard reactions with four carbohydrates, including arabinose (AN), sodium alginate (SA), maltodextrin (MD), and lactose (LT), and the corresponding conjugates were named BRG-AN, BRG-SA, BRG-MD, and BRG-LT, respectively. The formation of the BRG conjugates was confirmed by changes in the BRG amino groups, conjugation degree, as well as molecular weight. BRG-AN and BRG-MD presented a significantly higher conjugation degree and lower amino group levels compared to the other two conjugates. Circular dichroism (CD) analysis indicated that all the conjugated BRG displayed markedly decreased levels of β-sheets and increased levels of α-helixes. However, only BRG-AN increased significantly in irregular loops. Results from the Fourier Transform Infrared Spectroscopy (FTIR) analysis indicated that the most apparent changes in the structures of BRG conjugates were evident as absorption peaks at 3389 cm−1, 1528 cm−1, 1230 cm−1, and 953–1180 cm−1. After glycosylation, the solubility, emulsion activity index (EAI), and emulsion stability index (ESI) of BRG were significantly improved. After glycosylation of the BRG, induced by Maillard reactions with four carbohydrates, the denaturation temperature (Td) and enthalpy (ΔH) change values increased substantially from 90.16 °C to 124.28 °C and 11.01 J/g to 18.43 J/g, respectively. The results indicated that BRG-AN exhibited better solubility, EAI, and ESI than the other BRG conjugates.

Human liver CD8+ MAIT cells exert TCR/MR1-independent innate-like cytotoxicity in response to IL-15

Mucosal-associated invariant T (MAIT) cells, the most abundant innate-like T cells in the human liver, can be activated by cytokines during viral infection without TCR stimulation. Here, we examined the mechanisms underlying TCR/MR1-independent innate-like cytotoxicity of cytokine-activated liver MAIT cells. We also examined the phenotype and function of MAIT cells from patients with acute viral hepatitis. We obtained liver sinusoidal mononuclear cells from donor liver perfusate during liver transplantation and examined the effect of various cytokines on liver MAIT cells using flow cytometry and invitro cytotoxicity assays. We also obtained peripheral blood and liver-infiltrating T cells from patients with acute hepatitis A (AHA) and examined the phenotype and function of MAIT cells using flow cytometry. IL-15-stimulated MAIT cells exerted granzyme B-dependent innate-like cytotoxicity in the absence of TCR/MR1 interaction. PI3K-mTOR signaling, NKG2D ligation, and CD2-mediated conjugate formation were critically required for this IL-15-induced innate-like cytotoxicity. MAIT cells from patients with AHA exhibited activated and cytotoxic phenotypes with higher NKG2D expression. The innate-like cytotoxicity of MAIT cells was significantly increased in patients with AHA and correlated with serum alanine aminotransferase levels. Taken together, the results demonstrate that liver MAIT cells activated by IL-15 exert NKG2D-dependent innate-like cytotoxicity in the absence of TCR/MR1 engagement. Furthermore, the innate-like cytotoxicity of MAIT cells is associated with liver injury in patients with AHA, suggesting that MAIT cells contribute to immune-mediated liver injury. Immune-mediated liver injury commonly occurs during viral infections of the liver. Mucosal-associated invariant T (MAIT) cells are the most abundant innate-like T cells in the human liver. Herein, we have identified a mechanism by which MAIT cells circumvent conventional T cell receptor interactions to exert cytotoxicity. We show that this innate-like cytotoxicity is increased during acute hepatitis A virus infection and correlates with the degree of hepatocyte injury.

Platelets in Advanced Chronic Kidney Disease: Two Sides of the Coin.

Rates of thrombosis and bleeding episodes are both increased in patients with advanced chronic kidney disease (CKD). The pathogenic mechanisms of thrombosis in these patients include platelet activation, increased formation of platelet-leukocyte conjugates, and platelet-derived microparticles, as well as effects of uremic toxins on platelets. On the other side of the coin, platelet hyporeactivity mediated by uremic toxins and anemia contributes to the increased bleeding risk in advanced CKD. Platelets also contribute to the inflammatory environment, thus increasing the risk of cardiovascular diseases in these patients. This review provides insights into the altered platelet function in advanced stages of CKD and their relationship with risks of thrombosis and bleeding. Particularly, the effect of dialysis on platelets will be discussed. Furthermore, therapeutic options with respect to thrombotic disorders as well as bleeding in patients with CKD are reviewed.

Human Red Blood Cell Uptake and Sequestration of Arsenite and Selenite: Evidence for the Formation of a Protective Glutathione Conjugate

Over 200 million people worldwide are exposed to the proven human carcinogen, arsenic, in contaminated drinking water. In laboratory animals, arsenic and the essential trace element, selenium, can undergo mutual detoxification through the formation of the seleno‐bis(S‐glutathionyl) arsinium ion [(GS)2AsSe]−, which undergoes biliary and fecal elimination. [(GS)2AsSe]−, formed in animal red blood cells (RBCs), sequesters arsenic and selenium, and likely slows the distribution of both metalloids to the liver, and other organs susceptible to toxic effects. In human RBCs, the influence of arsenic on selenium accumulation, and vice versa, is largely unknown. The aims of this study were to characterize arsenite (AsIII) and selenite (SeIV) uptake by human RBCs, to determine if SeIV and AsIII increase the respective accumulation of the other in human RBCs, and ultimately to determine if this occurs through the formation and sequestration of [(GS)2AsSe]−. 75SeIV accumulation was inhibited by 4,4′‐diisothiocyanatodihydrostilbene‐2,2′‐disulfonic acid (H2DIDS) (IC50 1 ± 0.2 μM), suggesting uptake is mediated by the erythrocyte anion‐exchanger 1 (AE1 or Band 3, gene SLC4A1). HEK293 cells overexpressing AE1 showed concentration‐dependent 75SeIV uptake. 73AsIII uptake by human RBCs was temperature‐dependent and partly reduced by aquaglyceroporin 3 inhibitors. AsIII increased 75SeIV accumulation (in the presence of albumin) and SeIV increased 73AsIII accumulation in human RBCs. Near‐edge X‐ray absorption spectroscopy revealed the formation of [(GS)2AsSe]− in human RBCs exposed to both AsIII and SeIV. The sequestration of [(GS)2AsSe]− in human RBCs potentially slows arsenic distribution to susceptible tissues and could reduce arsenic‐induced disease.Support or Funding InformationCanadian Institutes of Health Research, Canada Research Chairs program, Natural Science and Engineering Council of Canada