RESUMO
The most commonly used flow cytometric (FCM) analysis of cellular DNA content relies on ethanol fixation followed by RNA digestion and propidium iodide (PI) intercalation into double-stranded DNA. This is a laborious and time-consuming procedure that is subject to systematic errors due to centrifugation and washing steps associated with sample preparation. It can adversely affect the reliability of the results. Here, we present a modified concept of DNA quantification in adherent cell lines by FCM that involves neither ethanol fixation nor any washing and cell transferring steps. Our high throughput assay of adherent cell lines reduces sample-processing time, requires minimal workload, provides a possibility for automation, and, if needed, also allows a significant reduction in the size of individual samples. Working with a well-proven commercial tool-The BD Cycletest™ Plus DNA Reagent Kit-primarily designed for cell cycle analysis and aneuploidy determination in experimental and clinical samples, we suggest a novel, very efficient, and robust approach for DNA research in adherent cell cultures.
Assuntos
DNA , Citometria de Fluxo , Humanos , Citometria de Fluxo/métodos , DNA/análise , Adesão Celular , Ciclo Celular/genética , Automação , Reprodutibilidade dos Testes , AneuploidiaRESUMO
In human cells, receptor-interacting protein kinase 2 (RIPK2) is mainly known to mediate downstream enzymatic cascades from the nucleotide-binding oligomerization domain-containing receptors 1 and 2 (NOD1/2), which are regulators of pro-inflammatory signaling. Thus, the targeted inhibition of RIPK2 has been proposed as a pharmacological strategy for the treatment of a variety of pathologies, in particular inflammatory and autoimmune diseases. In this work, we designed and developed novel thieno[2,3d]pyrimidine derivatives, in order to explore their activity and selectivity as RIPK2 inhibitors. Primary in vitro evaluations of the new molecules against purified RIPKs (RIPK1-4) demonstrated outstanding inhibitory potency and selectivity for the enzyme RIPK2. Moreover, investigations for efficacy against the RIPK2-NOD1/2 signaling pathways, conducted in living cells, showed their potency could be tuned towards a low nanomolar range. This could be achieved by solely varying the substitutions at position 6 of the thieno[2,3d]pyrimidine scaffold. A subset of lead inhibitors were ultimately evaluated for selectivity against 58 human kinases other than RIPKs, displaying great specificities. We therefore obtained new inhibitors that might serve as starting point for the preparation of targeted tools, which could be useful to gain a better understanding of biological roles and clinical potential of RIPK2.
Assuntos
Inflamação , Proteína Serina-Treonina Quinase 2 de Interação com Receptor , Transdução de Sinais , Humanos , Inflamação/tratamento farmacológico , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/antagonistas & inibidores , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/metabolismoRESUMO
Phytoprostanes (PhytoP) are natural products, which form in plants under oxidative stress conditions from α-linolenic acid. However, their epimers with relative prostaglandin configuration termed phytoglandins (PhytoG) have never been detected in Nature, likely because of the lack of synthetic reference material. Here, the first asymmetric total synthesis of such compounds, namely of PhytoGF1α (9-epi-16-F1t -PhytoP) and its diastereomer ent-16-epi-PhytoGF1α (ent-9,16-diepi-16-F1t -PhytoP), has been accomplished. The synthetic strategy is based on radical anion oxidative cyclization, copper(I)-mediated alkyl-alkyl coupling and enantioselective reduction reactions. A UHPLC-MS/MS study using the synthesized compounds as standards indicates PhytoG formation at significant levels during autoxidation of α-linolenic acid in edible vegetable oils. Initial testing of synthetic PhytoGs together with F1 -PhytoP and 15-F2t -IsoP derivatives for potential interactions with the PGF2α (FP) receptor did not reveal significant activity. The notion that PUFA-derived oxidatively formed cyclic metabolites with prostaglandin configuration do not form to a significant extent in biological or food matrices has to be corrected. Strong evidence is provided that oxidatively formed PhytoG metabolites may be ingested with plant-derived food, which necessitates further investigation of their biological profile.
Assuntos
Óleos de Plantas , Espectrometria de Massas em Tandem , Oxirredução , Prostaglandinas , VerdurasRESUMO
Candida albicans is the main causative agent of vulvovaginal candidiasis (VVC), a common mycosis in women, relapses of which are difficult to manage due to biofilm formation. This study aimed at developing novel non-toxic compounds active against Candida spp. biofilms. We synthesised analogues of natural antifungal peptides LL-III (LL-III/43) and HAL-2 (peptide VIII) originally isolated from bee venoms and elucidated their structures by nuclear magnetic resonance spectroscopy. The haemolytic, cytotoxic, antifungal and anti-biofilm activities of LL-III/43 and peptide VIII were then tested. LL-III/43 and VIII showed moderate cytotoxicity to HUVEC-2 cells and had comparable inhibitory activity against C. albicans and non-albicans spp. The lowest minimum inhibitory concentration (MIC90) of LL-III/43 was observed towards Candida tropicalis (0.8 µM). That was 8-fold lower than that of antimycotic amphotericin B. Both peptides can be used to inhibit Candida spp. bio film f ormation. Biofilm inhibitory concentrations (BIC50) ranged from 0.9 to 58.6 µM and biofilm eradication concentrations (BEC50) for almost all tested Candida spp. strains ranged from 12.8 to 200 µM. Als o pro ven were the peptides' abilities to reduce the area colonised by biofilms , inhibit hyphae formation and permeabilise cell membranes in biofil ms . LL-III/43 and VIII are promising candidates for further development as therapeutics against VVC.
Assuntos
Antifúngicos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Venenos de Abelha/química , Biofilmes/efeitos dos fármacos , Candida/efeitos dos fármacos , Anfotericina B/farmacologia , Antifúngicos/síntese química , Peptídeos Catiônicos Antimicrobianos/síntese química , Candidíase Vulvovaginal/microbiologia , Células Cultivadas , Feminino , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Hifas/efeitos dos fármacos , Testes de Sensibilidade MicrobianaRESUMO
We report on the synthesis of novel conformationally locked nucleoside and nucleotide derivatives, which are structurally closely related to clinically used antivirals such as didanosine and abacavir. As a suitable conformationally rigid substitute of the sugar/pseudosugar ring allowing a permanent stabilization of the nucleoside in North conformation we employed bicyclo[2.2.1]heptane (norbornane) substituted in the bridgehead position with a hydroxymethyl group and in the C-3 position with a nucleobase. Prepared nucleoside derivatives were also converted into appropriate phosphoramidate prodrugs (ProTides) in order to increase delivery of the compounds in the cells. All target compounds were evaluated in a broad antiviral and cytostatic assay panel.
Assuntos
Antivirais/síntese química , Norbornanos/química , Nucleosídeos/química , Nucleotídeos/química , Humanos , Norbornanos/síntese química , Conformação de Ácido Nucleico , Nucleosídeos/síntese química , Nucleotídeos/síntese química , EstereoisomerismoRESUMO
BACKGROUND: Apoptosis is one of the presumptive causes of CD4+ T cell depletion during HIV infection and progression to AIDS. However, the precise role of HIV-1 in this process remains unexplained. HIV-1 protease (PR) has been suggested as a possible factor, but a direct link between HIV-1 PR enzymatic activity and apoptosis has not been established. RESULTS: Here, we show that expression of active HIV-1 PR induces death in HeLa and HEK-293 cells via the mitochondrial apoptotic pathway. This conclusion is based on in vivo observations of the direct localization of HIV-1 PR in mitochondria, a key player in triggering apoptosis. Moreover, we observed an HIV-1 PR concentration-dependent decrease in mitochondrial membrane potential and the role of HIV-1 PR in activation of caspase 9, PARP cleavage and DNA fragmentation. In addition, in vitro data demonstrated that HIV-1 PR mediates cleavage of mitochondrial proteins Tom22, VDAC and ANT, leading to release of AIF and Hsp60 proteins. By using yeast two-hybrid screening, we also identified a new HIV-1 PR interaction partner, breast carcinoma-associated protein 3 (BCA3). We found that BCA3 accelerates p53 transcriptional activity on the bax promoter, thus elevating the cellular level of pro-apoptotic Bax protein. CONCLUSION: In summary, our results describe the involvement of HIV-1 PR in apoptosis, which is caused either by a direct effect of HIV-1 PR on mitochondrial membrane integrity or by its interaction with cellular protein BCA3.
Assuntos
Apoptose/genética , Infecções por HIV/metabolismo , Protease de HIV/metabolismo , HIV-1/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Fragmentação do DNA , Células HEK293 , Infecções por HIV/genética , Protease de HIV/genética , HIV-1/genética , Células HeLa , Humanos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Regiões Promotoras Genéticas/genética , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
Ghana's economy is climate sensitive as more than 80% of its agricultural production is rainfall dependent, with only 2% of irrigation potential used. This has consequences under changing climate, with the impact projected to intensify if things go in a business-as-usual scenario. The manifestation of climate change impact is evident in other sectors of the economy, which requires proactiveness to adapt and mitigate through the development and execution of national adaptation strategies. This research reviews the impact of climate change and some interventions made toward its management. The study explored peer-reviewed journals, policy documents, and technical reports for relevant materials that chronicle programmes and measures to address the challenges of climate change. The research revealed that Ghana had experienced about 1 °C rise in temperature over the past four decades and sea level rise with socioeconomic consequences including decreased agricultural productivity and inundation of coastal communities. Policy interventions have resulted in the introduction of several mitigative and adaptation programmes, such as building resilience in various economic sectors. The study highlighted the progress and challenges to climate change implementation programmes and future policy implementation plans. Inadequate funding of programmes and projects was identified as a critical challenge to achieving climate change policy goals and objectives. We recommend more political will from the government and stakeholders towards policy implementation and greater commitment to providing adequate funding for programmes and project implementation to ensure the success of local climate action for adaptation and mitigation, as well as for sustainable development.
RESUMO
Galectins, a class of carbohydrate-binding proteins, play a crucial role in various physiological and disease processes. Therefore, the identification of ligands that efficiently bind these proteins could potentially lead to the development of new therapeutic compounds. In this study, we present a method that involves screening synthetic click glycopeptide libraries to identify lectin-binding ligands with low micromolar affinity. Our methodology, initially optimized using Concanavalin A, was subsequently applied to identify binders for the therapeutically relevant galectin 1. Binding affinities were assessed using various methods and showed that the selected glycopeptides exhibited enhanced binding potency to the target lectins compared to the starting sugar moieties. This approach offers an alternative means of discovering galectin-binding ligands as well as other carbohydrate-binding proteins, which are considered important therapeutic targets.
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With the alarming increase in dying trees and massive logging in the Czech forests due to bark beetle infestation, the collection of non-wood forest products, a beneficial recreational activity in the Czech Republic, is now being promoted as an alternative to wood provisioning services. This paper aims to present findings on the non-wood forest product preferences in the country as part of a baseline assessment for promoting the usage. This study relied on the 2019 national survey data of public preferences in collecting forest berries, mushrooms, honey, and medicinal herbs. K-means cluster analysis was employed to classify the respondents. A binary logistic regression with a conditional forward approach was employed to identify the potential predictors of the high preference for each non-wood forest product. Data from 1,050 online respondents were included, and two groups of respondents were clustered based on their preferences for the entire non-wood forest, i.e., higher and lower utilization. The regression analysis revealed that frequent forest visitors were the primary predictor of high utilization of all non-wood forest products (between 1.437 to 4.579 odd ratios), in addition to age, gender, and location of the forest property. By clustering the respondents based on the high and low preferences in utilizing non-wood forest products, the promotion of this service, from recreational to potential livelihood activities and economic benefits, can be better targeted, e.g., target customer, infrastructure development in the location with high preferences, scenarios based on the type of owners (municipal or private forest owners), which in accordance to the national forest policy and laws, and, at the same time, maintain the ecological stability.
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Receptor-interacting protein kinases 2 and 3 (RIPK2 and RIPK3) are considered attractive therapeutic enzyme targets for the treatment of a multitude of inflammatory diseases and cancers. In this study, we developed three interrelated series of novel quinazoline-based derivatives to investigate the effects of extensive modifications of positions 6 and 7 of the central core on the inhibitory activity and the selectivity against these RIPKs. The design of the derivatives was inspired by analyses of available literary knowledge on both RIPK2 and RIPK3 in complex with known quinazoline or quinoline inhibitors. Enzymatic investigations for bioactivity of the prepared molecules against purified RIPKs (RIPK1-4) shed light on multiple potent and selective RIPK2 and dual RIPK2/3 inhibitors. Furthermore, evaluations in living cells against the RIPK2-NOD1/2-mediated signaling pathways, identified as the potential primary targets, demonstrated nanomolar inhibition for a majority of the compounds. In addition, we have demonstrated overall good stability of various lead inhibitors in both human and mouse microsomes and plasma. Several of these compounds also were evaluated for selectivity across 58 human kinases other than RIPKs, exhibiting outstanding specificity profiles. We have thus clearly demonstrated that tuning appropriate substitutions at positions 6 and 7 of the developed quinazoline derivatives may lead to interesting potency and specificities against RIPK2 and RIPK3. This knowledge might therefore be employed for the targeted preparation of new, highly potent and selective tools against these RIPKs, which could be of utility in biological and clinical research.
Assuntos
Microssomos , Quinazolinas , Humanos , Animais , Camundongos , Quinazolinas/farmacologia , Proteína Serina-Treonina Quinase 2 de Interação com ReceptorRESUMO
Ecosystem services are investigated from many perspectives, but there are very few studies comparing the perception of forest and demand for forest ecosystem services (FES) in a cross-cultural analysis. This study aims to map the demand for FES and find out the forest perception of forest visitors in both Czech and Chinese societies. Data were collected by structured questionnaire among three different groups of respondents (n = 847) in six forest areas. The questions were focused on the demand for FES, expectations from the forest, preference for the visual form of the forest, and the willingness of forest visitors. Analysis demonstrates that the demand for some FES is related to geographical and cultural conditions. The results indicated that provisioning and regulation services are perceived as more important than cultural services. The differences by country were obvious in the cultural and provisioning services: Chinese demand more relaxing and meditation activities, whereas Czech demand mushroom picking. A significant outcome is a high demand of Chinese respondents for recreational facilities. Tree planting was rated as one of the most popular voluntary activity across the whole sample. Meanwhile, some findings point to an increasing pressure on forest ecosystems and their protection, which emerge due to the strong demand for recreational facilities. According to the findings, active involvement of forest visitors in various activities is recommended so that their appreciation of FES will constantly increase and to take into account the profile of visitors and incorporate them in forest management and planning in order to meet societal demand.
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A unified approach to meroterpenoids applanatumols B, V, W, X, and Y produced by the medicinal fungus Ganoderma applanatum and 2'-epi-spiroapplanatumine O is presented. The key synthetic sequence consists of a tandem anionic ketone allylation/oxy-Cope rearrangement/α-oxygenation furnishing an α-aminoxy ketone and a persistent radical effect-based 5-exo-trig cyclization leading to the trisubstituted cyclopentane core. The relative configuration of applanatumol V has to be revised. Some compounds display significant cytotoxic and antioxidant properties.
Assuntos
Ganoderma , Antioxidantes , Ciclização , CetonasRESUMO
This article presents the current status of the development of bioeconomy in the Czech Republic. Although the country has no unified strategy on bioeconomy, there are ambitious governmental innovation strategies and focused strategies for each region. Traditionally, the country has had a strong research performance in chemistry and biology, which together with developed agriculture, forestry and food industries, provides a good foundation for the development of locally based circular systems. Moreover, the government supports research on tools and applications of new plant breeding technologies, including genome editing, and there is a strong initiative from the research community calling to update EU regulatory policy in this area.
Assuntos
Biotecnologia/economia , Conservação dos Recursos Naturais/economia , Agricultura/economia , República Tcheca , Desenvolvimento Econômico , União Europeia , Indústria Alimentícia/economia , Agricultura Florestal/economiaRESUMO
Cryptococcosis is an invasive infection that accounts for 15% of AIDS-related fatalities. Still, treating cryptococcosis remains a significant challenge due to the poor availability of effective antifungal therapies and emergence of drug resistance. Interestingly, protease inhibitor components of antiretroviral therapy regimens have shown some clinical benefits in these opportunistic infections. We investigated Major aspartyl peptidase 1 (May1), a secreted Cryptococcus neoformans protease, as a possible target for the development of drugs that act against both fungal and retroviral aspartyl proteases. Here, we describe the biochemical characterization of May1, present its high-resolution X-ray structure, and provide its substrate specificity analysis. Through combinatorial screening of 11,520 compounds, we identified a potent inhibitor of May1 and HIV protease. This dual-specificity inhibitor exhibits antifungal activity in yeast culture, low cytotoxicity, and low off-target activity against host proteases and could thus serve as a lead compound for further development of May1 and HIV protease inhibitors.
Assuntos
Antifúngicos/química , Ácido Aspártico Proteases/antagonistas & inibidores , Cryptococcus neoformans/enzimologia , Proteínas Fúngicas/antagonistas & inibidores , Antifúngicos/metabolismo , Antifúngicos/farmacologia , Ácido Aspártico Proteases/genética , Ácido Aspártico Proteases/metabolismo , Sítios de Ligação , Domínio Catalítico , Cristalografia por Raios X , Avaliação Pré-Clínica de Medicamentos , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Fungos/efeitos dos fármacos , HIV/enzimologia , Protease de HIV/química , Protease de HIV/metabolismo , Simulação de Dinâmica Molecular , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Relação Estrutura-Atividade , Especificidade por SubstratoRESUMO
A broad variety of central nervous system diseases have been associated with glutamate induced excitotoxicity under pathological conditions. The neuroprotective effects of neurosteroids can combat this excitotoxicity. Herein, we have demonstrated the neuroprotective effect of novel steroidal N-methyl-D-aspartate receptor inhibitors against glutamate- or NMDA- induced excitotoxicity. Pretreatment with neurosteroids significantly reduced acute L-glutamic acid or NMDA excitotoxicity mediated by Ca2+ entry and consequent ROS (reactive oxygen species) release and caspase-3 activation. Compounds 6 (IC50 = 5.8 µM), 7 (IC50 = 12.2 µM), 9 (IC50 = 7.8 µM), 13 (IC50 = 1.1 µM) and 16 (IC50 = 8.2 µM) attenuated glutamate-induced Ca2+ entry more effectively than memantine (IC50 = 18.9 µM). Moreover, compound 13 shows comparable effect with MK-801 (IC50 = 1.2 µM) and also afforded significant protection without any adverse effect upon prolonged exposure. This drop in Ca2+ level resulted in corresponding ROS suppression and prevented glutamate-induced caspase-3 activation. Therefore, compound 13 has great potential for development into a therapeutic agent for improving glutamate-related nervous system diseases.
Assuntos
Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Neurotransmissores/farmacologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Animais , Células Cultivadas , Ácido Glutâmico/efeitos adversos , N-Metilaspartato/efeitos adversos , Neurônios/citologia , Neurônios/metabolismo , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/química , Neurotransmissores/química , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismoRESUMO
Two molecules of mistaken identity are addressed. Uncovering these assignment errors led us to formulate more general guidelines about additional misassignments in cases of published bis-imines derived from 1,2-phenylenediamine and hydroxybenzaldehydes having no substituent in ortho-positions. The main purpose of this article is to highlight this repetitive assignment error in the literature and thus increase the likelihood of correct assignments in future papers.
Assuntos
DNA/química , Quadruplex GRESUMO
Diphosphates of the antiviral acyclic nucleoside phosphonates (ANPs) were evaluated in telomeric repeat amplification protocol (TRAP) for their ability to inhibit the extension of telomeres by human telomerase. Extracts from human leukaemia HL-60 cells were used as a source of the enzyme. Data show that the most effective compound studied was the guanine derivative PMEGpp (IC50 12.7+/-0.5 micromolL(-1) at 125 micromolL(-1) deoxynucleoside triphosphates (dNTPs)). The inhibitory effects of other PME, PMP and HPMP diphosphates on telomerase reverse transcriptase decreased in the order: (R)-PMPGpp>(R)-HPMPGpp>PMEDAPpp>(S)-PMPGpp>(S)-HPMPApp>PMEO-DAPypp>(R)-6-cyprPMPDAPpp>(R)-PMPApp>(R)-PMPDAPpp> or =PMEApp> or =PMECpp>PMETpp>(S)-PMPApp approximately 6-Me2PMEDAPpp. These results are consistent with the observed antineoplastic activities of the parental guanine (PMEG) and 2,6-diaminopurine (PMEDAP) PME-derivatives. Moreover, structure-activity relationship indicates enantioselectivity of some of these human telomerase inhibitors: (R)-isomers of the PMP-derivatives possess stronger inhibitory potency towards the enzyme than (S)-isomers. The data may contribute to the rational design of telomerase inhibitors based on the structure of acyclic nucleotide analogues.
Assuntos
Organofosfonatos/farmacologia , Telomerase/antagonistas & inibidores , Sequência de Bases , Primers do DNA , Células HL-60 , HumanosRESUMO
Core-shell nanoparticles based on fluorescent nanodiamonds coated with a biocompatible N-(2-hydroxypropyl)methacrylamide copolymer shell were developed for background-free near-infrared imaging of cancer cells. The particles showed excellent colloidal stability in buffers and culture media. After conjugation with a cyclic RGD peptide they selectively targeted integrin αvß3 receptors on glioblastoma cells with high internalization efficacy.
Assuntos
Integrina alfaVbeta3/metabolismo , Nanodiamantes/química , Peptídeos Cíclicos/química , Acrilamidas/química , Materiais Biocompatíveis/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Química Click , Endocitose , Corantes Fluorescentes/química , Glioma/metabolismo , Glioma/patologia , Humanos , Integrina alfaVbeta3/química , Microscopia Confocal , Nanodiamantes/toxicidade , Peptídeos Cíclicos/metabolismo , Dióxido de Silício/químicaRESUMO
Targeted biocompatible nanostructures with controlled plasmonic and morphological parameters are promising materials for cancer treatment based on selective thermal ablation of cells. Here, core-shell plasmonic nanodiamonds consisting of a silica-encapsulated diamond nanocrystal coated in a gold shell are designed and synthesized. The architecture of particles is analyzed and confirmed in detail using electron tomography. The particles are biocompatibilized using a PEG polymer terminated with bioorthogonally reactive alkyne groups. Azide-modified transferrin is attached to these particles, and their high colloidal stability and successful targeting to cancer cells overexpressing the transferrin receptor are demonstrated. The particles are nontoxic to the cells and they are readily internalized upon binding to the transferrin receptor. The high plasmonic cross section of the particles in the near-infrared region is utilized to quantitatively ablate the cancer cells with a short, one-minute irradiation by a pulse 750-nm laser.
Assuntos
Técnicas de Ablação/métodos , Nanodiamantes/química , Materiais Biocompatíveis/farmacocinética , Carbocianinas/química , Ouro/química , Células HeLa/efeitos dos fármacos , Humanos , Hipertermia Induzida/métodos , Terapia a Laser/métodos , Terapia de Alvo Molecular/métodos , Nanopartículas/química , Nanoconchas/química , Polietilenoglicóis/química , Receptores da Transferrina/metabolismo , Transferrina/química , Transferrina/farmacologiaRESUMO
Helquat dyes are the first helicene-like cationic styryl dyes obtained as separate enantiomers. Their remarkable chiroptical properties are due to the unique combination of a cationic hemicyanine chromophore and a helicene-like motif. The magnitude of the ECD response and the pH switching along with their positioning in the visible region are unprecedented among helicenoids.