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The efficacy of boron neutron capture therapy relies on the selective delivery of boron carriers to malignant cells. p‐Boronophenylalanine (BPA), a boron delivery agent, has been proposed to be localized to cells through transporter‐mediated mechanisms. In this study, we screened aromatic amino acid transporters to identify BPA transporters. Human aromatic amino acid transporters were functionally expressed in Xenopus oocytes and examined for BPA uptake and kinetic parameters. The roles of the transporters in BPA uptake were characterized in cancer cell lines. For the quantitative assessment of BPA uptake, HPLC was used throughout the study. Among aromatic amino acid transporters, ATB0,+, LAT1 and LAT2 were found to transport BPA with Km values of 137.4 ± 11.7, 20.3 ± 0.8 and 88.3 ± 5.6 μM, respectively. Uptake experiments in cancer cell lines revealed that the LAT1 protein amount was the major determinant of BPA uptake at 100 μM, whereas the contribution of ATB0,+ became significant at 1000 μM, accounting for 20–25% of the total BPA uptake in MCF‐7 breast cancer cells. ATB0,+, LAT1 and LAT2 transport BPA at affinities comparable with their endogenous substrates, suggesting that they could mediate effective BPA uptake in vivo. The high and low affinities of LAT1 and ATB0,+, respectively, differentiate their roles in BPA uptake. ATB0,+, as well as LAT1, could contribute significantly to the tumor accumulation of BPA at clinical dose. Chromatograms of BPA taken up by aromatic amino acid transporters. ATB0,+, LAT1 and LAT2 transport BPA.

Heteroatom-rich organoboron compounds have attracted attention as modulators of enzyme function. Driven by the unmet need to develop chemoselective access to boron chemotypes, we report herein the synthesis of α- and β-aminocyano(MIDA)boronates from borylated carbonyl compounds. Activity-based protein profiling of the resulting β-aminoboronic acids furnishes selective and cell-active inhibitors of the (ox)lipid-metabolizing enzyme α/β-hydrolase domain 3 (ABHD3). The most potent compound displays nanomolar in vitro and in situ IC 50 values and fully inhibits ABHD3 activity in human cells with no detectable cross-reactivity against other serine hydrolases. These findings demonstrate that synthetic methods that enhance the heteroatom diversity of boron-containing molecules within a limited set of scaffolds accelerate the discovery of chemical probes of human enzymes. Heteroatom-rich organoboron compounds are promising modulators of enzyme activity. Here, the authors report a library of aminocyanoboronates as serine hydrolases inhibitors with the most potent compound showing in vivo and in vitro nanomolar activity and high selectivity towards human ABHD3 hydrolase.

Both limiting and toxic soil concentrations of the essential micronutrient boron represent major limitations to crop production worldwide. We identified Bot1, a BOR1 ortholog, as the gene responsible for the superior boron-toxicity tolerance of the Algerian barley landrace Sahara 3771 (Sahara). Bot1 was located at the tolerance locus by high-resolution mapping. Compared to intolerant genotypes, Sahara contains about four times as many Bot1 gene copies, produces substantially more Bot1 transcript, and encodes a Bot1 protein with a higher capacity to provide tolerance in yeast. Bot1 transcript levels identified in barley tissues are consistent with a role in limiting the net entry of boron into the root and in the disposal of boron from leaves via hydathode guttation.

Boron (B) is a unique micronutrient for plants given that the range of B concentration from its essentiality to toxicity is extremely narrow, and also because it occurs as an uncharged molecule (boric acid) which can pass lipid bilayers without any degree of controls, as occurs for other ionic nutrients. Boron frequently exceeds the plant’s requirement in arid and semiarid environments due to poor drainage, and in agricultural soils close to coastal areas due to the intrusion of B-rich seawater in fresh aquifer or because of dispersion of seawater aerosol. Global releases of elemental B through weathering, volcanic and geothermal processes are also relevant in enriching B concentration in some areas. Considerable progress has been made in understanding how plants react to B toxicity and relevant efforts have been made to investigate: (I) B uptake and in planta partitioning, (II) physiological, biochemical, and molecular changes induced by B excess, with particular emphasis to the effects on the photosynthetic process, the B-triggered oxidative stress and responses of the antioxidant apparatus to B toxicity, and finally (III) mechanisms of B tolerance. Recent findings addressing the effects of B toxicity are reviewed here, intending to clarify the effect of B excess and to propose new perspectives aimed at driving future researches on the topic.

Boron neutron capture therapy (BNCT) is a promising cancer binary therapy modality that utilizes the nuclear capture reaction of thermal neutrons by boron-10 resulting in a localized release of high- and low-linear energy transfer (LET) radiation. Electrochemotherapy (ECT) is based on electroporation (EP) that induces opening of pores in cell membranes, allowing the entry of compounds. Because EP is applied locally to a tumor, the compound is incorporated preferentially by tumor cells. Based on the knowledge that the therapeutic success of BNCT depends centrally on the boron content in tumor and normal tissues and that EP has proven to be an excellent facilitator of tumor biodistribution of an anti-tumor agent, the aim of this study was to evaluate if EP can optimize the delivery of boronated compounds. We performed biodistribution studies and qualitative microdistribution analyses of boron employing the boron compound sodium decahydrodecaborate (GB-10) + EP in the hamster cheek pouch oral cancer model. Syrian hamsters with chemically induced exophytic squamous cell carcinomas were used. A typical EP treatment was applied to each tumor, varying the moment of application with respect to the administration of GB-10 (early or late). The results of this study showed a significant increase in the absolute and relative tumor boron concentration and optimization of the qualitative microdistribution of boron by the use of early EP + GB-10 versus GB-10 without EP. This strategy could be a tool to improve the therapeutic efficacy of BNCT/GB-10 in vivo.

Background: Boron neutron capture therapy requires a 2 mM 10B concentration in the tumor. The well-known BNCT patient treatment method using boronophenylalanine (BPA) as a boron-carrying agent utilizes [18F]fluoroBPA ([18F]FBPA) as an agent to qualify for treatment. Precisely, [18F]FBPA must have at least a 3:1 tumor to background tissue ratio to qualify the patient for BNCT treatment. Normal, hyperplasia, and cancer thyroids capture iodine and several other large ions, including BF4−, through a sodium-iodine symporter (NIS) expressed on the cell surface in normal conditions. In cancer, NIS is also expressed within the thyroid cell and is not functional. Methods: To visualize the thyroids and NIS, we have used a [18F]NaBF4 positron emission tomography (PET) tracer. It was injected into the tail veins of rats. The [18F]NaBF4 PET tracer was produced from NaBF4 by the isotopic exchange of natural 19F with radioactive 18F. Rats were subject to hyperplasia and tumor-inducing treatment. The NIS in thyroids was visualized by immunofluorescence staining. The boron concentration was calculated from Standard Uptake Values (SUV) in the PET/CT images and from the production data. Results: 41 MBq, 0.64 pmol of [18F]NaBF4 PET tracer that contained 0.351 mM, 53 nmol of NaBF4 was injected into the tail vein. After 17 min, the peak activity in the thyroid reached 2.3 MBq/mL (9 SUVmax). The natB concentration in the thyroid with hyperplasia reached 381 nM. Conclusions: Such an incorporation would require an additional 110 mg/kg dose of [10B]NaBF4 to reach the necessary 2 mM 10B concentration in the tumor. For future BNCT treatments of thyroid cancer, contrary to the 131I used now, there is no post-treatment radioactive decay, the patient can be immediately discharged from hospital, and there is no six-month moratorium for pregnancy. This method can be used for BNCT treatment compounds of the type R-BFn, where 1 <= n <= 3, labeled with 18F relatively easily, as in our example. A patient may undergo injection of a mixture of nonradioactive R-BFn to reach the necessary 10B concentration for BNCT treatment in the tumor together, with [18F]R-BFn for boron mapping.

A genetically encoded platform can produce chiral organoboranes in bacteria with high turnover, enantioselectivity and chemoselectivity, and can be tuned and configured through DNA manipulation. Biocatalysed boranes Boron is embedded in the synthesis of organic molecules, for example as the metal catalyst in cross-coupling chemistry, and organoboron compounds are important chemotherapeutics. However, boron is rare in nature and no enzymes that catalyse the formation of carbon–boron (C–B) bonds are known. In this work, Frances Arnold and colleagues report the directed evolution of cytochrome c enzymes from Rhodothermus marinus to develop whole-cell biocatalysts for the synthesis of C–B bonds in Escherichia Coli . The evolved enzymes catalyse the insertion of carbene reagents into the boron–hydrogen bonds of boranes to give chiral organoboranes (either enantiomer) with high levels of stereocontrol. The scope of this transformation includes CF 3 -substituted products, a motif used in pharmaceuticals. These whole-cell reactions could potentially be incorporated into both natural and engineered metabolic pathways. Recent advances in enzyme engineering and design have expanded nature’s catalytic repertoire to functions that are new to biology 1 , 2 , 3 . However, only a subset of these engineered enzymes can function in living systems 4 , 5 , 6 , 7 . Finding enzymatic pathways that form chemical bonds that are not found in biology is particularly difficult in the cellular environment, as this depends on the discovery not only of new enzyme activities, but also of reagents that are both sufficiently reactive for the desired transformation and stable in vivo . Here we report the discovery, evolution and generalization of a fully genetically encoded platform for producing chiral organoboranes in bacteria. Escherichia coli cells harbouring wild-type cytochrome c from Rhodothermus marinus 8 ( Rma cyt c ) were found to form carbon–boron bonds in the presence of borane–Lewis base complexes, through carbene insertion into boron–hydrogen bonds. Directed evolution of Rma cyt c in the bacterial catalyst provided access to 16 novel chiral organoboranes. The catalyst is suitable for gram-scale biosynthesis, providing up to 15,300 turnovers, a turnover frequency of 6,100 h –1 , a 99:1 enantiomeric ratio and 100% chemoselectivity. The enantiopreference of the biocatalyst could also be tuned to provide either enantiomer of the organoborane products. Evolved in the context of whole-cell catalysts, the proteins were more active in the whole-cell system than in purified forms. This study establishes a DNA-encoded and readily engineered bacterial platform for borylation; engineering can be accomplished at a pace that rivals the development of chemical synthetic methods, with the ability to achieve turnovers that are two orders of magnitude (over 400-fold) greater than those of known chiral catalysts for the same class of transformation 9 , 10 , 11 . This tunable method for manipulating boron in cells could expand the scope of boron chemistry in living systems.

TCH4 is a xyloglucan endotransglucosylase/hydrolase (XTH) family member. Extensive studies have shown that XTHs are very important in cell wall homeostasis for plant growth and development. Boron (B), as an essential micronutrient for plants, plays an essential role in the cross-linking of cell wall pectin. However, the effect of B on cell wall organization is unclear. This study aimed to explore the mechanism of plant adaption to B stress by investigating the role of TCH4 in cell wall homeostasis. We conducted both plate and hydroponic cultures of wild-type Col-0 and overexpression and gene knockout lines of XTH22/TCH4 to analyze the phenotype, components, and characteristics of the cell wall using immunofluorescence, atomic force microscopy (AFM), and transmission electron microscopy (TEM). B deficiency induces the expression of TCH4. The overexpression lines of TCH4 presented more sensitivity to B deficiency than the wild-type Col-0, while the knockout lines of TCH4 were more resistant to low B stress. Up-regulation of TCH4 influenced the ratio of chelator-soluble pectin to alkali-soluble pectin and decreased the degree of methylesterification of pectin under B-deficient conditions. Moreover, we found that B deficiency disturbed the arrangement of cellulose, enlarged the gap between cellulose microfibrils, and decreased the mechanical strength of the cell wall, leading to the formation of a thickened and deformed triangular region of the cell wall. These symptoms were more profound in the TCH4 overexpression lines. Consistently, compared with Col-0, the O2− and MDA contents in the TCH4 overexpression lines increased under B-deficient conditions. This study identified the B-deficiency-induced TCH4 gene, which regulates cell wall homeostasis to influence plant growth under B-deficient conditions.

Boron is an essential mineral that plays an important role in several biological processes. Boron is required for growth of plants, animals, and humans. There are increasing evidences of this nutrient showing a variety of pleiotropic effects, ranging from anti-inflammatory and antioxidant effects to the modulation of different body systems. In the past few years, the trials showed disease-related polymorphisms of boron in different species, which has drawn attention of scientists to the significance of boron to health. Low boron profile has been related with poor immune function, increased risk of mortality, osteoporosis, and cognitive deterioration. High boron status revealed injury to cell and toxicity in different animals and humans. Some studies have shown some benefits of higher boron status, but findings have been generally mixed, which perhaps accentuates the fact that dietary intake will benefit only if supplemental amount is appropriate. The health benefits of boron are numerous in animals and humans; for instance, it affects the growth at safe intake. Central nervous system shows improvement and immune organs exhibit enhanced immunity with boron supplementation. Hepatic metabolism also shows positive changes in response to dietary boron intake. Furthermore, animals and human fed diets supplemented with boron reveal improved bone density and other benefits including embryonic development, wound healing, and cancer therapy. It has also been reported that boron affects the metabolism of several enzymes and minerals. In the background of these health benefits, low or high boron status is giving cause for concern. Additionally, researches are needed to further elucidate the mechanisms of boron effects, and determine the requirements in different species.