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The Journal of Physical Chemistry. B Oct 2021Therapeutic preparations of insulin often contain phenolic molecules, which can impact both pharmacokinetics and shelf life. Thus, understanding the interactions of...
Therapeutic preparations of insulin often contain phenolic molecules, which can impact both pharmacokinetics and shelf life. Thus, understanding the interactions of insulin and phenolic molecules can aid in designing improved therapeutics. In this study, we use molecular dynamics to investigate phenol release from the insulin hexamer. Leveraging recent advances in methods for analyzing molecular dynamics data, we expand on existing simulation studies to identify and quantitatively characterize six phenol binding/unbinding pathways for wild-type and A10 Ile → Val and B13 Glu → Gln mutant insulins. A number of these pathways involve large-scale opening of the primary escape channel, suggesting that the hexamer is much more dynamic than previously appreciated. We show that phenol unbinding is a multipathway process, with no single pathway representing more than 50% of the reactive current and all pathways representing at least 10%. We use the mutant simulations to show how the contributions of specific pathways can be rationally manipulated. Predicting the net effects of mutations is more challenging because the kinetics depend on all of the pathways, demanding quantitatively accurate simulations and experiments.
Topics: Insulin; Kinetics; Phenol; Phenols
PubMed: 34648712
DOI: 10.1021/acs.jpcb.1c06544 -
Microbiology Spectrum Dec 2023Aromatic compounds are globally abundant organic molecules with a multitude of natural and anthropogenic sources, underpinning the relevance of their biodegradation....
Aromatic compounds are globally abundant organic molecules with a multitude of natural and anthropogenic sources, underpinning the relevance of their biodegradation. EbN1 is a well-studied environmental betaproteobacterium specialized on the anaerobic degradation of aromatic compounds. The here studied responsiveness toward phenol in conjunction with the apparent high ligand selectivity (non-promiscuity) of its PheR sensor and those of the related -cresol (PcrS) and -ethylphenol (EtpR) sensors are in accord with the substrate-specificity and biochemical distinctiveness of the associated degradation pathways. Furthermore, the present findings advance our general understanding of the substrate-specific regulation of the strain's remarkable degradation network and of the concentration thresholds below which phenolic compounds become essentially undetectable and as a consequence should escape substantial biodegradation. Furthermore, the findings may inspire biomimetic sensor designs for detecting and quantifying phenolic contaminants in wastewater or environments.
Topics: Phenol; Phenols; Rhodocyclaceae; Biodegradation, Environmental; Anaerobiosis
PubMed: 37823660
DOI: 10.1128/spectrum.02100-23 -
ACS Chemical Biology Sep 2021Membrane protein structures provide a fundamental understanding of their molecular actions and are of importance for drug development. Detergents are widely used to...
Membrane protein structures provide a fundamental understanding of their molecular actions and are of importance for drug development. Detergents are widely used to solubilize, stabilize, and crystallize membrane proteins, but membrane proteins solubilized in conventional detergents are prone to denaturation and aggregation. Thus, developing novel detergents with enhanced efficacy for protein stabilization remains important. We report herein the design and synthesis of a class of phenol-derived maltoside detergents. Using two different linkers, we prepared two sets of new detergents, designated maltose-bis(hydroxymethyl)phenol (MBPs) and maltose-tris(hydroxymethyl)phenol (MTPs). The evaluation of these detergents with three transporters and two G-protein coupled receptors allowed us to identify a couple of new detergents (MBP-C9 and MTP-C12) that consistently conferred enhanced stability to all tested proteins compared to a gold standard detergent (DDM). Furthermore, the data analysis based on the detergent structures provides key detergent features responsible for membrane protein stabilization that together will facilitate the future design of novel detergents.
Topics: Detergents; Glycolipids; Hydrophobic and Hydrophilic Interactions; Membrane Transport Proteins; Phenol; Protein Conformation; Protein Denaturation; Protein Stability; Receptors, G-Protein-Coupled; Structure-Activity Relationship; Thermodynamics
PubMed: 34445864
DOI: 10.1021/acschembio.1c00578 -
International Journal of Hygiene and... Mar 2023Early life environmental exposures may affect bone mass accrual in childhood, but only one study has assessed the role of environmental phenols on child bone health.
BACKGROUND
Early life environmental exposures may affect bone mass accrual in childhood, but only one study has assessed the role of environmental phenols on child bone health.
METHODS
We used data from 223 mother-child dyads enrolled in the Health Outcomes and Measures of the Environment (HOME) Study (Cincinnati, OH; 2003-2006). We quantified benzophenone-3, bisphenol A (BPA), 2,5-dichlorophenol, and triclosan in maternal urine collected at 16- and 26-weeks gestation and calculated the average of creatinine-adjusted concentrations. We performed dual x-ray absorptiometry at age 12 years and calculated Z-scores for whole body (less head), total hip, femoral neck, and 1/3rd distal radius bone mineral content (BMC) and areal bone mineral density (aBMD) as well as ultra-distal radius aBMD and spine BMC and bone mineral apparent density (BMAD). We estimated covariate-adjusted associations per doubling of maternal urinary environmental phenol concentrations in linear regression models. We also examined effect measure modification by child's sex and estimated associations of the environmental phenol mixture with BMC and aBMD using quantile g-computation.
RESULTS
We observed generally null associations for all analytes and bone measures. Yet, in adjusted models, higher urinary 2,5-dichlorophenol concentrations were associated with higher 1/3rd distal radius BMC (β: 0.09; 95% CI: 0.02, 0.17) and aBMD (β: 0.09; 95% CI: 0.02, 0.17) Z-scores in the overall sample. In sex-stratified analyses, the magnitude of the BMC association was positive for females (β: 0.16; 95% CI: 0.06, 0.26) and null for males (β: 0.02; 95% CI: 0.08, 0.13). The environmental phenol mixture was associated with greater 1/3rd distal radius BMC and aBMD Z-scores in both sexes, which was mostly driven by benzophenone-3 in males and 2,5-dichlorophenol in females.
CONCLUSION
In this prospective cohort study, we observed generally null associations for environmental phenols with BMC and aBMD at age 12 years. While there was a positive association of 2,5-dichlorophenol concentrations during fetal development with distal radius BMC and aBMD at age 12 years, future studies utilizing methods capable of differentiating cortical and trabecular bone are needed to elucidate potential mechanisms and implications for bone strength and microarchitecture.
Topics: Male; Female; Humans; Child; Bone Density; Prospective Studies; Phenol
PubMed: 36525700
DOI: 10.1016/j.ijheh.2022.114104 -
Drug Design, Development and Therapy 2022Lonapegsomatropin, a long-acting GH therapy (LAGH), was approved by the United States Food and Drug Administration in August 2021 for the treatment of pediatric growth... (Review)
Review
Lonapegsomatropin, a long-acting GH therapy (LAGH), was approved by the United States Food and Drug Administration in August 2021 for the treatment of pediatric growth hormone deficiency (GHD). Lonapegsomatropin is a prodrug consisting of unmodified GH transiently conjugated to methoxypolyethylene glycol which enables time-release of GH with a half-life of ~25 hours allowing for once-weekly administration. Clinical trials of lonapegsomatropin have demonstrated positive efficacy results in children (phase 2 and 3) and adults (phase 2) with GHD. The phase 3 trial in children with GHD established non-inferiority and statistical superiority of height velocity with lonapegsomatropin (11.2 cm/yr) compared to daily GH (10.3 cm/yr), with no concerning side effects with lonapegsomatropin. Similar growth responses have been reported in other LAGH products in phase 2 (somapacitan) and phase 3 (somatrogon) trials. Lonapegsomatropin is distributed in temperature-stable, prefilled cartridges at 9 different doses that can be prescribed based upon specific weight brackets designed to deliver approximately 0.24 mg/kg/wk. An electronic delivery device is required to combine the powdered medication with the diluent and deliver the medication subcutaneously through a small gauge needle to the recipient. The pharmacodynamic data from the clinical trials of lonapegsomatropin has been used to develop models to estimate an average IGF-1 value drawn at any time during the weekly injection interval. This average IGF-1 value may be used to for safety monitoring and/or to guide dose adjustment. New LAGH products, including lonapegsomatropin, may potentially improve patient adherence, quality of life and clinical outcomes, particularly in patients with poor adherence to daily GH injections in the future. With the availability of new LAGH products, clinicians will need to identify the best candidates for LAGH therapy and understand how to monitor and adjust therapy. Long-term surveillance studies are needed to demonstrate adherence, efficacy, cost-effectiveness and safety of LAGH preparations.
Topics: Adult; Child; Dwarfism, Pituitary; Histidine; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Mannitol; Phenol; Quality of Life; United States
PubMed: 35791404
DOI: 10.2147/DDDT.S336285 -
International Journal of Molecular... May 2023A number of novel di- and triorganotin(IV) complexes - (PhSnL, PhSnL, EtSnL, PhSnL, PhSnL) with mono- or dianionic forms of thio-Schiff bases containing antioxidant...
A number of novel di- and triorganotin(IV) complexes - (PhSnL, PhSnL, EtSnL, PhSnL, PhSnL) with mono- or dianionic forms of thio-Schiff bases containing antioxidant sterically hindered phenol or catechol fragments were synthesized. Compounds - were characterized by H, C NMR, IR spectroscopy, and elemental analysis. The molecular structures of complexes and in the crystal state were established by single-crystal X-ray analysis. The antioxidant activity of new complexes as radical scavengers was estimated in DPPH and ABTS assays. It was found that compounds and with free phenol or catechol fragments are more active in these tests than complexes - with tridentate O,N,S-coordinated ligands. The effect of compounds - on the promoted oxidative damage of the DNA by 2,2'-azobis(2-amidinopropane) dihydrochloride and in the process of rat liver (Wistar) homogenate lipid peroxidation in vitro was determined. Complexes and were characterized by more pronounced antioxidant activity in the reaction of lipid peroxidation in vitro than compounds -. The antiproliferative activity of compounds - was investigated against MCF-7, HTC-116, and A-549 cell lines by an MTT test. The values of IC are significantly affected by the presence of free antioxidant fragments and the coordination site for binding.
Topics: Rats; Animals; Antioxidants; Phenol; Schiff Bases; Rats, Wistar; Organotin Compounds; Phenols; Catechols; Coordination Complexes; Ligands
PubMed: 37176027
DOI: 10.3390/ijms24098319 -
Molecules (Basel, Switzerland) Aug 2022Phenol is an important chemical material that is widely used in industry. Currently, phenol is dominantly produced by the well-known three-step cumene process, which... (Review)
Review
Phenol is an important chemical material that is widely used in industry. Currently, phenol is dominantly produced by the well-known three-step cumene process, which suffers from severe drawbacks. Therefore, developing a green, sustainable, and economical strategy for the production of phenol directly from benzene is urgently needed. In recent years, the photocatalytic hydroxylation of benzene to phenol, which is economically feasible and could be performed under mild conditions, has attracted more attention, and development of highly efficient photocatalyst would be a key issue in this field. In this review, we systematically introduce the recent achievements of photocatalytic hydroxylation of benzene to phenol from 2015 to mid-2022, and various heterogeneous photocatalysts are comprehensively reviewed, including semiconductors, polyoxometalates (POMs), graphitic carbon nitride (g-CN), metal-organic frameworks (MOFs), carbon materials, and some other types of photocatalysts. Much effort is focused on the physical and chemical approaches for modification of these photocatalysts. The challenges and future promising directions for further enhancing the catalytic performances in photocatalytic hydroxylation of benzene are discussed in the end.
Topics: Benzene; Catalysis; Hydroxylation; Phenol; Phenols
PubMed: 36080224
DOI: 10.3390/molecules27175457 -
BioMed Research International 2016Sesame (Sesamum indicum L.) seeds are popular nutritional food but with limited knowledge about their antioxidant and antiproliferative activities of various varieties....
Sesame (Sesamum indicum L.) seeds are popular nutritional food but with limited knowledge about their antioxidant and antiproliferative activities of various varieties. Phytochemical profiles and antioxidant and antiproliferative activities of six varieties of sesame (Sesamum indicum L.) seeds were studied. Fenheizhi3 (black) cultivar exhibited the maximum contents of total phenolics and lignans and values of total oxygen radical absorbance capacity (ORAC) and antiproliferative activity (EC50) against HepG2 cells. Bound ORAC values showed strong associations with bound phenolics contents (r = 0.976, p < 0.01); in bound phenolic extracts, EC50 values showed strong negative associations with phenolic contents (r = -0.869, p < 0.05) and ORAC values (r = -0.918, p < 0.01). Moreover, the contents of free phenolics were higher than that of the bound phenolics, and the three black sesame seeds generally depicted higher total phenolics compared to the three white varieties. The antioxidant (ORAC values) and antiproliferation activities of six sesame seeds were both associated with contents of bound phenolics (r > 0.8, p < 0.05). Interestingly, nonlignan components in bound phenolics contributed to the antioxidant and antiproliferative activities. This study suggested that Fenheizhi3 variety is superior to the other five varieties as antioxidant supplements.
Topics: Antioxidants; Cell Line, Tumor; Cell Proliferation; Hep G2 Cells; Humans; Lignans; Oxygen Radical Absorbance Capacity; Phenol; Phytochemicals; Plant Extracts; Seeds; Sesamum
PubMed: 27597975
DOI: 10.1155/2016/8495630 -
Molecules (Basel, Switzerland) Mar 2022Plant polyphenols, such as the African potato ()-derived bis-catechol rooperol, can display promising anticancer activity yet suffer from rapid metabolism. Embarking...
Plant polyphenols, such as the African potato ()-derived bis-catechol rooperol, can display promising anticancer activity yet suffer from rapid metabolism. Embarking upon a program to systematically examine potentially more metabolically stable replacements for the catechol rings in rooperol, we report here a general, scalable synthesis of rooperol and analogues that builds on our previous synthetic approach incorporating a key Pd-catalyzed decarboxylative coupling strategy. Using this approach, we have prepared and evaluated the cancer cell cytotoxicity of rooperol and a series of analogues. While none of the analogues examined here were superior to rooperol in preventing the growth of cancer cells, analogues containing phenol or methylenedioxyphenyl replacements for one or both catechol rings were nearly as effective as rooperol.
Topics: Catechols; Neoplasms; Phenol; Phenols; Polyphenols
PubMed: 35335155
DOI: 10.3390/molecules27061792 -
European Journal of Nutrition Feb 2023(Poly)phenols are bioactive compounds widely distributed in plant-based foods. Currently, limited data exist on the intake distribution of (poly)phenols across meals....
PURPOSE
(Poly)phenols are bioactive compounds widely distributed in plant-based foods. Currently, limited data exist on the intake distribution of (poly)phenols across meals. This study aimed to estimate dietary intakes of all individual (poly)phenols and total intake per class and subclass by meal event, and to identify their main food sources in the subcohort MAX from the Diet, Cancer and Health-Next Generations cohort (DCH-NG).
METHODS
Dietary data were collected using three web-based 24-h dietary recalls over 1 year. In total, 676 participants completed at least one recall. The dietary data were linked to Phenol-Explorer database using standardized procedures and an in-house software. We categorized foods/drinks into five options of meal events selected by the participant: 'Breakfast', 'Lunch', 'Evening', 'Snack', and 'Drink'.
RESULTS
Adjusted total (poly)phenols mean intake by meal was the highest in the drink event (563 mg/day in men and 423 mg/day in women) and the lowest in the evening event (146 mg/day in men and 137 mg/day in women). The main overall (poly)phenol class contributor was phenolic acids (55.7-79.0%), except for evening and snack events where it was flavonoids (45.5-60%). The most consumed (poly)phenol subclasses were hydroxycinnamic acids and proanthocyanidins. Nonalcoholic beverages (coffee accounted for 66.4%), cocoa products, and cereals were the main food sources of total (poly)phenols.
CONCLUSION
This study provides data on the variability in the intake of classes and subclasses of (poly)phenols and their main food sources by meal event according to lifestyle data, age, and gender in a Danish population.
Topics: Male; Humans; Female; Phenol; Polyphenols; Phenols; Diet; Neoplasms
PubMed: 35994085
DOI: 10.1007/s00394-022-02977-x