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1.
Carbohydr Polym ; 338: 122172, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38763719

RESUMO

Polysaccharide-based hydrogels are promising for many biomedical applications including drug delivery, wound healing, and tissue engineering. We illustrate herein self-healing, injectable, fast-gelling hydrogels prepared from multi-reducing end polysaccharides, recently introduced by the Edgar group. Simple condensation of reducing ends from multi-reducing end alginate (M-Alg) with amines from polyethylene imine (PEI) in water affords a dynamic, hydrophilic polysaccharide network. Trace amounts of acetic acid can accelerate the gelation time from hours to seconds. The fast-gelation behavior is driven by rapid Schiff base formation and strong ionic interactions induced by acetic acid. A cantilever rheometer enables real-time monitoring of changes in viscoelastic properties during hydrogel formation. The reversible nature of these crosslinks (imine bonds, ionic interactions) provides a hydrogel with low toxicity in cell studies as well as self-healing and injectable properties. Therefore, the self-healing, injectable, and fast-gelling M-Alg/PEI hydrogel holds substantial promise for biomedical, agricultural, controlled release, and other applications.


Assuntos
Alginatos , Hidrogéis , Polissacarídeos , Alginatos/química , Hidrogéis/química , Hidrogéis/síntese química , Hidrogéis/farmacologia , Polissacarídeos/química , Polietilenoimina/química , Humanos , Reologia , Animais , Bases de Schiff/química , Injeções , Camundongos
2.
ACS Med Chem Lett ; 15(3): 349-354, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38505851

RESUMO

Next generation antimicrobial therapeutics are desperately needed as new pathogens with multiple resistance mechanisms continually emerge. Two oxaboroles, tavaborole and crisaborole, were recently approved as topical treatments for onychomycosis and atopic dermatitis, respectively, warranting further studies into this privileged structural class. Herein, we report the antimicrobial properties of 3-substituted-2(5H)-oxaboroles, an unstudied family of medicinally relevant oxaboroles. Our results revealed minimum inhibitory concentrations as low as 6.25 and 5.20 µg/mL against fungal (e.g., Penicillium chrysogenum) and yeast (Saccharomyces cerevisiae) pathogens, respectively. These oxaboroles were nonhemolytic and nontoxic to rat myoblast cells (H9c2). Structure-activity relationship studies suggest that planarity is important for antimicrobial activity, possibly due to the effects of extended conjugation between the oxaborole and benzene rings.

3.
Angew Chem Int Ed Engl ; 63(6): e202317699, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38168073

RESUMO

In an effort to synthesize chemically recyclable thermoplastic elastomers, a redox-switchable catalytic system was developed to synthesize triblock copolymers containing stiff poly(lactic acid) (PLA) end blocks and a flexible poly(tetrahydrofuran-co-cyclohexene oxide) (poly(THF-co-CHO) copolymer as the mid-block. The orthogonal reactivity induced by changing the oxidation state of the iron-based catalyst enabled the synthesis of the triblock copolymers in a single reaction flask from a mixture of monomers. The triblock copolymers demonstrated improved flexibility compared to poly(l-lactic acid) (PLLA) and thermomechanical properties that resemble thermoplastic elastomers, including a rubbery plateau in the range of -60 to 40 °C. The triblock copolymers containing a higher percentage of THF versus CHO were more flexible, and a blend of triblock copolymers containing PLLA and poly(d-lactic acid) (PDLA) end-blocks resulted in a stereocomplex that further increased polymer flexibility. Besides the low cost of lactide and THF, the sustainability of this new class of triblock copolymers was also supported by their depolymerization, which was achieved by exposing the copolymers sequentially to FeCl3 and ZnCl2 /PEG under reactive distillation conditions.

4.
Macromol Biosci ; 24(1): e2300138, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37326828

RESUMO

Gasotransmitters, gaseous signaling molecules including nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2 S), maintain myriad physiological processes. Low levels of gasotransmitters are often associated with specific problems or diseases, so NO, CO, and H2 S hold potential in treating bacterial infections, chronic wounds, myocardial infarction, ischemia, and various other diseases. However, their clinical applications as therapeutic agents are limited due to their gaseous nature, short half-life, and broad physiological roles. One route toward the greater application of gasotransmitters in medicine is through localized delivery. Hydrogels are attractive biomedical materials for the controlled release of embedded therapeutics as they are typically biocompatible, possess high water content, have tunable mechanical properties, and are injectable in certain cases. Hydrogel-based gasotransmitter delivery systems began with NO, and hydrogels for CO and H2 S have appeared more recently. In this review, the biological importance of gasotransmitters is highlighted, and the fabrication of hydrogel materials is discussed, distinguishing between methods used to physically encapsulate small molecule gasotransmitter donor compounds or chemically tether them to a hydrogel scaffold. The release behavior and potential therapeutic applications of gasotransmitter-releasing hydrogels are also detailed. Finally, the authors envision the future of this field and describe challenges moving forward.


Assuntos
Gasotransmissores , Sulfeto de Hidrogênio , Gasotransmissores/fisiologia , Gasotransmissores/uso terapêutico , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/uso terapêutico , Óxido Nítrico , Monóxido de Carbono/farmacologia , Monóxido de Carbono/uso terapêutico , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico
5.
Proc Natl Acad Sci U S A ; 120(41): e2204700120, 2023 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-37796990

RESUMO

Neurobiological consequences of traumatic brain injury (TBI) result from a complex interplay of secondary injury responses and sequela that mediates chronic disability. Endothelial cells are important regulators of the cerebrovascular response to TBI. Our work demonstrates that genetic deletion of endothelial cell (EC)-specific EPH receptor A4 (EphA4) using conditional EphA4f/f/Tie2-Cre and EphA4f/f/VE-Cadherin-CreERT2 knockout (KO) mice promotes blood-brain barrier (BBB) integrity and tissue protection, which correlates with improved motor function and cerebral blood flow recovery following controlled cortical impact (CCI) injury. scRNAseq of capillary-derived KO ECs showed increased differential gene expression of BBB-related junctional and actin cytoskeletal regulators, namely, A-kinase anchor protein 12, Akap12, whose presence at Tie2 clustering domains is enhanced in KO microvessels. Transcript and protein analysis of CCI-injured whole cortical tissue or cortical-derived ECs suggests that EphA4 limits the expression of Cldn5, Akt, and Akap12 and promotes Ang2. Blocking Tie2 using sTie2-Fc attenuated protection and reversed Akap12 mRNA and protein levels cortical-derived ECs. Direct stimulation of Tie2 using Vasculotide, angiopoietin-1 memetic peptide, phenocopied the neuroprotection. Finally, we report a noteworthy rise in soluble Ang2 in the sera of individuals with acute TBI, highlighting its promising role as a vascular biomarker for early detection of BBB disruption. These findings describe a contribution of the axon guidance molecule, EphA4, in mediating TBI microvascular dysfunction through negative regulation of Tie2/Akap12 signaling.


Assuntos
Barreira Hematoencefálica , Lesões Encefálicas Traumáticas , Receptor EphA4 , Animais , Camundongos , Proteínas de Ancoragem à Quinase A/genética , Proteínas de Ancoragem à Quinase A/metabolismo , Barreira Hematoencefálica/metabolismo , Lesões Encefálicas Traumáticas/genética , Lesões Encefálicas Traumáticas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Células Endoteliais/metabolismo , Camundongos Knockout , Receptor TIE-2/genética , Receptor TIE-2/metabolismo , Receptor EphA4/genética , Receptor EphA4/metabolismo
6.
Nat Commun ; 14(1): 3635, 2023 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-37336876

RESUMO

Cryptic sites are short signaling peptides buried within the native extracellular matrix (ECM). Enzymatic cleavage of an ECM protein reveals these hidden peptide sequences, which interact with surface receptors to control cell behavior. Materials that mimic this dynamic interplay between cells and their surroundings via cryptic sites could enable application of this endogenous signaling phenomenon in synthetic ECM hydrogels. We demonstrate that depsipeptides ("switch peptides") can undergo enzyme-triggered changes in their primary sequence, with proof-of-principle studies showing how trypsin-triggered primary sequence rearrangement forms the bioadhesive pentapeptide YIGSR. We then engineered cryptic site-mimetic synthetic ECM hydrogels that experienced a cell-initiated gain of bioactivity. Responding to the endothelial cell surface enzyme aminopeptidase N, the inert matrix transformed into an adhesive synthetic ECM capable of supporting endothelial cell growth. This modular system enables dynamic reciprocity in synthetic ECMs, reproducing the natural symbiosis between cells and their matrix through inclusion of tunable hidden signals.


Assuntos
Matriz Extracelular , Peptídeos , Matriz Extracelular/metabolismo , Peptídeos/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Células Endoteliais , Hidrogéis/metabolismo
9.
Angew Chem Int Ed Engl ; 62(26): e202303755, 2023 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-37194941

RESUMO

We report three constitutionally isomeric tetrapeptides, each comprising one glutamic acid (E) residue, one histidine (H) residue, and two lysine (KS ) residues functionalized with side-chain hydrophobic S-aroylthiooxime (SATO) groups. Depending on the order of amino acids, these amphiphilic peptides self-assembled in aqueous solution into different nanostructures:nanoribbons, a mixture of nanotoroids and nanoribbons, or nanocoils. Each nanostructure catalyzed hydrolysis of a model substrate, with the nanocoils exhibiting the greatest rate enhancement and the highest enzymatic efficiency. Coarse-grained molecular dynamics simulations, analyzed with unsupervised machine learning, revealed clusters of H residues in hydrophobic pockets along the outer edge of the nanocoils, providing insight for the observed catalytic rate enhancement. Finally, all three supramolecular nanostructures catalyzed hydrolysis of the l-substrate only when a pair of enantiomeric Boc-l/d-Phe-ONp substrates were tested. This study highlights how subtle molecular-level changes can influence supramolecular nanostructures, and ultimately affect catalytic efficiency.


Assuntos
Nanoestruturas , Nanotubos de Carbono , Peptídeos/química , Nanoestruturas/química , Isomerismo , Catálise
10.
Angew Chem Int Ed Engl ; 62(22): e202302303, 2023 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-37078735

RESUMO

Inducing high levels of reactive oxygen species (ROS) inside tumor cells is a cancer therapy method termed chemodynamic therapy (CDT). Relying on delivery of Fenton reaction promoters such as Fe2+ , CDT takes advantage of overproduced ROS in the tumor microenvironment. We developed a peptide-H2 S donor conjugate, complexed with Fe2+ , termed AAN-PTC-Fe2+ . The AAN tripeptide was specifically cleaved by legumain, an enzyme overexpressed in glioma cells, to release carbonyl sulfide (COS). Hydrolysis of COS by carbonic anhydrase formed H2 S, an inhibitor of catalase, an enzyme that detoxifies H2 O2 . Fe2+ and H2 S together increased intracellular ROS levels and decreased viability in C6 glioma cells compared with controls lacking either Fe2+ , the AAN sequence, or the ability to generate H2 S. AAN-PTC-Fe2+ performed better than temezolimide while exhibiting no cytotoxicity toward H9C2 cardiomyocytes. This study provides an H2 S-amplified, enzyme-responsive platform for synergistic cancer treatment.


Assuntos
Glioma , Nanopartículas , Neoplasias , Humanos , Espécies Reativas de Oxigênio , Peptídeos/farmacologia , Linhagem Celular Tumoral , Microambiente Tumoral , Peróxido de Hidrogênio
11.
BMC Vet Res ; 19(1): 52, 2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36797726

RESUMO

BACKGROUND: Hydrogen sulfide (H2S) donors are crucial tools not only for understanding the role of H2S in cellular function but also as promising therapeutic agents for oxidative stress-related diseases. This study aimed to explore the effect of amino acid-derived N-thiocarboxyanhydrides (NTAs), which release physiological H2S levels in the presence of carbonic anhydrase, on porcine sperm function during short-term incubation with and without induced oxidative stress. For this purpose, we employed two H2S-releasing NTAs with release half-lives (t1/2) in the range of hours that derived from the amino acids glycine (Gly-NTA) or leucine (Leu-NTA). Because carbonic anhydrase is crucial for H2S release from NTAs, we first measured the activity of this enzyme in the porcine ejaculate. Then, we tested the effect of Gly- and Leu-NTAs at 10 and 1 nM on sperm mitochondrial activity, plasma membrane integrity, acrosomal status, motility, motile subpopulations, and redox balance during short-term incubation at 38 °C with and without a reactive oxygen species (ROS)-generating system. RESULTS: Our results show that carbonic anhydrase is found both in spermatozoa and seminal plasma, with activity notably higher in the latter. Both Gly- and Leu-NTAs did not exert any noxious effects, but they enhanced sperm mitochondrial activity in the presence and absence of oxidative stress. Moreover, NTAs (except for Leu-NTA 10 nM) tended to preserve the sperm redox balance against the injuries provoked by oxidative stress, which provide further support to the antioxidant effect of H2S on sperm function. Both compounds also increased progressive motility over short-term incubation, which may translate into prolonged sperm survival. CONCLUSIONS: The presence of carbonic anhydrase activity in mammalian spermatozoa makes NTAs promising molecules to investigate the role of H2S in sperm biology. For the first time, beneficial effects of NTAs on mitochondrial activity have been found in mammalian cells in the presence and absence of oxidative stress. NTAs are interesting compounds to investigate the role of H2S in sperm mitochondria-dependent events and to develop H2S-related therapeutic protocols against oxidative stress in assisted reproductive technologies.


Assuntos
Aminoácidos , Anidrases Carbônicas , Masculino , Animais , Suínos , Aminoácidos/metabolismo , Sementes/metabolismo , Espermatozoides , Estresse Oxidativo , Mitocôndrias , Espécies Reativas de Oxigênio/metabolismo , Anidrases Carbônicas/metabolismo , Anidrases Carbônicas/farmacologia , Mamíferos
12.
J Biol Chem ; 298(10): 102402, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35988644

RESUMO

Hydrogen sulfide (H2S) is produced endogenously by several enzymatic pathways and modulates physiological functions in mammals. Quantification of H2S in biochemical systems remains challenging because of the presence of interferents with similar reactivity, particularly thiols. Herein, we present a new quantification method based on the formation of pyrene excimers in solution. We synthesized the probe 2-(maleimido)ethyl 4-pyrenylbutanoate (MEPB) and determined that MEPB reacted with H2S in a two-step reaction to yield the thioether-linked dimer (MEPB)2S, which formed excimers upon excitation, with a broad peak of fluorescence emission centered at 480 nm. In contrast, we found that the products formed with thiols showed peaks at 378 and 398 nm. The difference in emission between the products prevented the interference. Furthermore, we showed that the excimer fluorescence signal yielded a linear response to H2S, with a limit of detection of 54 nM in a fluorometer. Our quantification method with MEPB was successfully applied to follow the reaction of H2S with glutathione disulfide and to quantify the production of H2S from cysteine by Escherichia coli. In conclusion, this method represents an addition to the toolkit of biochemists to quantify H2S specifically and sensitively in biochemical systems.


Assuntos
Corantes Fluorescentes , Sulfeto de Hidrogênio , Pirenos , Cisteína , Corantes Fluorescentes/química , Sulfeto de Hidrogênio/análise , Sulfeto de Hidrogênio/química , Pirenos/química , Compostos de Sulfidrila/química , Fluorescência
13.
ACS Appl Mater Interfaces ; 14(25): 28628-28638, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35715217

RESUMO

Tissue-engineered constructs are currently limited by the lack of vascularization necessary for the survival and integration of implanted tissues. Hydrogen sulfide (H2S), an endogenous signaling gas (gasotransmitter), has been recently reported as a promising alternative to growth factors to mediate and promote angiogenesis in low concentrations. Yet, sustained delivery of H2S remains a challenge. Herein, we have developed angiogenic scaffolds by covalent attachment of an H2S donor to a polycaprolactone (PCL) electrospun scaffold. These scaffolds were engineered to include azide functional groups (on 1, 5, or 10% of the PCL end groups) and were modified using a straightforward click reaction with an alkyne-functionalized N-thiocarboxyanhydride (alkynyl-NTA). This created H2S-releasing scaffolds that rely on NTA ring-opening in water followed by conversion of released carbonyl sulfide into H2S. These functionalized scaffolds showed dose-dependent release of H2S based on the amount of NTA functionality within the scaffold. The NTA-functionalized fibrous scaffolds supported human umbilical vein endothelial cell (HUVEC) proliferation, formed more confluent endothelial monolayers, and facilitated the formation of tight cell-cell junctions to a greater extent than unfunctionalized scaffolds. Covalent conjugation of H2S donors to scaffolds not only promotes HUVEC proliferation in vitro, but also increases neovascularization in ovo, as observed in the chick chorioallantoic membrane assay. NTA-functionalized scaffolds provide localized control over vascularization through the sustained delivery of a powerful endogenous angiogenic agent, which should be further explored to promote angiogenesis in tissue engineering.


Assuntos
Sulfeto de Hidrogênio , Animais , Membrana Corioalantoide , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Sulfeto de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/farmacologia , Neovascularização Fisiológica , Engenharia Tecidual , Alicerces Teciduais
14.
ACS Appl Bio Mater ; 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35505454

RESUMO

Stimuli-responsive peptide-based biomaterials are increasingly gaining interest for various specific and targeted treatments, including drug delivery and tissue engineering. Among all stimuli, pH can be especially useful because endogenous pH changes are often associated with abnormal microenvironments. pH-Responsive amino acids and organic linkers can be easily incorporated into peptides that self-assemble into various nanostructures. Thus, these largely biocompatible and easily tunable platforms are ideal candidates for drug release and as fibrous materials capable of mimicking the native extracellular matrix. In this review, we highlight common design motifs and mechanisms of pH-responsiveness in self-assembling peptide-based biomaterials, focusing on recent advances of these biomaterials applied in drug delivery and tissue engineering. Finally, we suggest future challenges and areas for potential development in pH-responsive self-assembling peptide-based biomaterials.

15.
Chem Commun (Camb) ; 58(34): 5225-5228, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35380568

RESUMO

Herein, the synthetic methods for preparation of a novel light-responsive metal-organic framework (MOF) UiO-AZB-F are outlined. Upon irradiation with green light, the framework demonstrates controlled release of chemotherapeutic drug cargo with simultaneous breakdown into low toxicity small molecule components.


Assuntos
Neoplasias Colorretais , Estruturas Metalorgânicas , Neoplasias Colorretais/tratamento farmacológico , Portadores de Fármacos , Humanos
16.
J Vasc Interv Radiol ; 33(1): 78-85, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34563699

RESUMO

The optimal medical management of patients following endovascular deep venous interventions remains ill-defined. As such, the Society of Interventional Radiology Foundation (SIRF) convened a multidisciplinary group of experts in a virtual Research Consensus Panel (RCP) to develop a prioritized research agenda regarding antithrombotic therapy following deep venous interventions. The panelists presented the gaps in knowledge followed by discussion and ranking of research priorities based on clinical relevance, overall impact, and technical feasibility. The following research topics were identified as high priority: 1) characterization of biological processes leading to in-stent stenosis/rethrombosis; 2) identification and validation of methods to assess venous flow dynamics and their effect on stent failure; 3) elucidation of the role of inflammation and anti-inflammatory therapies; and 4) clinical studies to compare antithrombotic strategies and improve venous outcome assessment. Collaborative, multicenter research is necessary to answer these questions and thereby enhance the care of patients with venous disease.


Assuntos
Radiologia Intervencionista , Doenças Vasculares , Consenso , Humanos , Pesquisa , Doenças Vasculares/diagnóstico por imagem , Doenças Vasculares/terapia , Procedimentos Cirúrgicos Vasculares
17.
ACS Chem Biol ; 16(7): 1128-1141, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34114796

RESUMO

Hydrogen sulfide (H2S) has gained significant attention as a potent bioregulator in the redox metabolome, but it is just one of many reactive sulfur species (RSS). Recently, small molecule persulfides (structure RSSH) have emerged as RSS of particular interest due to their enhanced antioxidant abilities compared to H2S and their ability to directly convert protein thiols into protein persulfides, suggesting that persulfides may have distinct physiological functions from H2S. However, persulfides exhibit instability and cross-reactivity that hampers the elucidation of their precise biological roles. As such, chemists have designed chemical tools and techniques to facilitate the study of persulfides under various conditions. These molecules and methods include persulfide trapping reagents and sensors, as well as compounds that degrade in response to various triggers to release persulfides, termed persulfide donors. There now exist a variety of persulfide donor classes, some of which possess tissue-targeting capabilities designed to mimic localized endogenous production of RSS. This Review briefly covers the physicochemical properties of persulfides, the endogenous production of small molecule persulfides, and their reactions with protein thiols and other reactive species. These introductory sections are followed by a discussion of chemical tools used in persulfide chemical biology, with critical analysis of recent advancements in the field and commentary on potential directions for future research.


Assuntos
Sulfetos/análise , Sulfetos/farmacologia , Animais , Linhagem Celular Tumoral , Técnicas de Química Analítica , Dissulfetos/química , Dissulfetos/metabolismo , Dissulfetos/efeitos da radiação , Humanos , Indicadores e Reagentes/química , Luz , Oxirredução , Pró-Fármacos/química , Pró-Fármacos/metabolismo , Pró-Fármacos/farmacologia , Pró-Fármacos/efeitos da radiação , Sulfetos/química , Sulfetos/metabolismo
18.
Chem Commun (Camb) ; 57(45): 5522-5525, 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-33956024

RESUMO

A library of N-thiocarboxyanhydrides (NTAs) derived from natural amino acids with benign byproducts and controlled H2S-release kinetics is reported. Minimal acute in vitro toxicity was observed in multiple cell lines, while longer-term toxicity in cancer cells was observed, with slow-releasing donors exhibiting the greatest cytotoxic effects.


Assuntos
Aminoácidos/química , Anidridos/química , Antineoplásicos/química , Sulfeto de Hidrogênio/química , Bibliotecas de Moléculas Pequenas/química , Anidridos/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Técnicas Eletroquímicas , Células HT29 , Humanos , Cinética , Células MCF-7 , Bibliotecas de Moléculas Pequenas/farmacologia , Relação Estrutura-Atividade
19.
Angew Chem Int Ed Engl ; 60(11): 6061-6067, 2021 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-33511734

RESUMO

Persulfides (R-SSH) have been hypothesized as potent redox modulators and signaling compounds. Reported herein is the synthesis, characterization, and in vivo evaluation of a persulfide donor that releases N-acetyl cysteine persulfide (NAC-SSH) in response to the prokaryote-specific enzyme nitroreductase. The donor, termed NDP-NAC, decomposed in response to E. coli nitroreductase, resulting in release of NAC-SSH. NDP-NAC elicited gastroprotective effects in mice that were not observed in animals treated with control compounds incapable of persulfide release or in animals treated with Na2 S. NDP-NAC induced these effects by the upregulation of beneficial small- and medium-chain fatty acids and through increasing growth of Turicibacter sanguinis, a beneficial gut bacterium. It also decreased the populations of Synergistales bacteria, opportunistic pathogens implicated in gastrointestinal infections. This study reveals the possibility of maintaining gut health or treating microbiome-related diseases by the targeted delivery of reactive sulfur species.


Assuntos
Antibacterianos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Pró-Fármacos/farmacologia , Sulfetos/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Desenho de Fármacos , Escherichia coli/efeitos dos fármacos , Cinética , Listeria monocytogenes/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pró-Fármacos/síntese química , Pró-Fármacos/química , Staphylococcus aureus/efeitos dos fármacos , Sulfetos/síntese química , Sulfetos/química
20.
ACS Macro Lett ; 10(12): 1460-1466, 2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-35549146

RESUMO

The controlled synthesis of polymers containing densely grafted cyclodextrin units has proven challenging due to the steric hindrance of these cyclic oligosaccharides. In this study, we report the controlled synthesis of poly(ß-cyclodextrin) [poly(ß-CD)] through ring-opening metathesis polymerization (ROMP) using Grubbs third-generation catalyst. Molecular weights of >105 g/mol were obtained with dispersity values (D) of ≤1.2. In aqueous solution, ß-cyclodextrin forms a host-guest complex with adamantyl groups (Ad). These interactions were utilized to prepare supramolecular polymer networks (SPNs) made by adding poly(ß-CD) to α,ω-adamantyl-functionalized poly(2-hydroxyethyl acrylate) (Ad-PHEA-Ad). These poly(ß-CD)/Ad-PHEA-Ad SPNs were prepared in aqueous solution and then dried to make homogeneous, transparent films. Varying the ratios of the two components enabled structure-property studies via tensile measurements.


Assuntos
Ciclodextrinas , beta-Ciclodextrinas , Polimerização , Polímeros , Propilenoglicóis , Água
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