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1.
Zootaxa ; 5231(5): 552-566, 2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-37045126

RESUMO

A species of Trichotylenchus nematode was isolated from the rhizosphere of banana root in Leizhou City, Guangdong Province, China. The species assumes the following characteristics: open C-shaped body; head offset from body; lateral field with three incisures, pharyngeal and tail regions irregularly areolated; stylet 18.6-20.7 µm long; pharyngeal gland not extending over intestine; fibrous tissue present in the intestine; post-anal intestinal sac present; elongate-subcylindroid tail, bluntly conoid terminus, lack of striations, and containing 34-44 annuli. In addition, scanning electron microscopy was used to elucidate some morphological details, but only some juveniles were observed. Partial 18S rRNA, ITS, and 28S D2-D3 expansion sequences were amplified with universal primers and deposited in GenBank under accession numbers ON622716, ON622717, and ON622714, respectively. Here, this species was identified as T. dispersus [(Siddiqi & Sharma, 1995) Geraert, 2011].


Assuntos
Tylenchoidea , Animais , Tylenchoidea/genética , Rizosfera , China , Bases de Dados de Ácidos Nucleicos
2.
Cell Mol Life Sci ; 80(4): 102, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36939886

RESUMO

Forkhead box O3 is a protein encoded by the FOXO3 gene expressed throughout the body. FOXO3 could play a crucial role in longevity and many other pathologies, such as Alzheimer's disease, glioblastoma, and stroke. This study is a comprehensive review of the expression of FOXO3 under ischemia and reperfusion (IR) and the molecular mechanisms of its regulation and function. We found that the expression level of FOXO3 under ischemia and IR is tissue-specific. Specifically, the expression level of FOXO3 is increased in the lung and intestinal epithelial cells after IR. However, FOXO3 is downregulated in the kidney after IR and in the skeletal muscles following ischemia. Interestingly, both increased and decreased FOXO3 expression have been reported in the brain, liver, and heart following IR. Nevertheless, these contribute to stimulating ischemia and reperfusion injury via the induction of inflammatory response, apoptosis, autophagy, mitophagy, pyroptosis, and oxidative damage. These results suggest that FOXO3 could play protective effects in some organs and detrimental effects in others against IR injury. Most importantly, these findings indicate that controlling FOXO3 expression, genetically or pharmacologically, could contribute to preventing or treating ischemia and reperfusion damage.


Assuntos
Traumatismo por Reperfusão , Humanos , Proteína Forkhead Box O3/genética , Proteína Forkhead Box O3/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Apoptose/genética , Estresse Oxidativo , Isquemia
3.
Adv Mater ; 35(19): e2210936, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36810927

RESUMO

Antimicrobial agents are massively used to disinfect the pathogen contaminated surfaces since the Corona Virus Disease 2019 (COVID-19) outbreak. However, their defects of poor durability, strong irritation, and high environmental accumulation are exposed. Herein, a convenient strategy is developed to fabricate long-lasting and target-selective antimicrobial agent with the special hierarchical structure through bottom-up assembly of natural gallic acid with arginine surfactant. The assembly starts from rodlike micelles, further stacking into hexagonal columns and finally interpenetrating into spherical assemblies, which avoid explosive release of antimicrobial units. The assemblies show anti-water washing and high adhesion on various surfaces; and thus, possess highly efficient and broad-spectrum antimicrobial activities even after using up to eleven cycles. Both in vitro and in vivo experiments prove that the assemblies are highly selective in killing pathogens without generating toxicity. The excellent antimicrobial virtues well satisfy the increasing anti-infection demands and the hierarchical assembly exhibits great potential as a clinical candidate.


Assuntos
Anti-Infecciosos , COVID-19 , Tensoativos , Arginina , Polifenóis/farmacologia , Anti-Infecciosos/farmacologia , Plantas
4.
Nano Lett ; 23(1): 371-379, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36441573

RESUMO

Antibacterial amphiphiles normally kill bacteria by destroying the bacterial membrane. Whether and how antibacterial amphiphiles alter normal cell membrane and lead to subsequent effects on pathogen invasion into cells have been scarcely promulgated. Herein, by taking four antibacterial gemini amphiphiles with different spacer groups to modulate cell-mimic phospholipid giant unilamellar vesicles (GUVs), bacteria adhesion on the modified GUVs surface and bacteria engulfment process by the GUVs are clearly captured by confocal laser scanning microscopy. Further characterization shows that the enhanced cationic surface charge of GUVs by the amphiphiles determines the bacteria adhesion amount, while the involvement of amphiphile in GUVs results in looser molecular arrangement and concomitant higher fluidity in the bilayer membranes, facilitating the bacteria intruding into GUVs. This study sheds new light on the effect of amphiphiles on membrane bilayer and the concurrent effect on pathogen invasion into cell mimics and broadens the nonprotein-mediated endocytosis pathway for live bacteria.


Assuntos
Aderência Bacteriana , Fluidez de Membrana , Fosfolipídeos , Lipossomas Unilamelares , Bactérias/metabolismo , Antibacterianos/farmacologia
5.
J Colloid Interface Sci ; 615: 395-407, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35150952

RESUMO

Smart artificial viruses have been successfully developed by co-assembly of de novo designed peptides with DNA, which achieved stimuli-responsibility and efficient gene transfection in cancer cells. The peptides were designed to incorporate several functional segments, including a hydrophobic aromatic segment to drive self-assembly, two or more cysteines to regulate the assemblage shape and stabilize the assembled nanostructures via forming disulfide bonds, several lysines to facilitate co-assembly with DNA and binding to cell membranes, and an enzyme-cleavable segment to introduce cancer sensitivity. The rationally designed peptides self-assembled into stable nanospheres with a uniform diameter of < 10 nm, which worked as capsid-like subunits to further interact with DNA to produce hierarchical virus-mimicking structures by encapsulating DNA in the interior. Such artificial viruses can effectively protect DNA from nuclease digestion and achieve efficient genome release by enzyme-triggered structure disassembly, which ensured a high level of gene transfection in tumor cells. The system emulates very well the structural and functional properties of natural viruses from the aspects of capsid formation, genome package and gene transfection, which is highly promising for application as efficient gene vectors.


Assuntos
Capsídeo , Nanosferas , Partículas Artificiais Semelhantes a Vírus , Capsídeo/química , DNA/química , Peptídeos/química
6.
Angew Chem Int Ed Engl ; 61(6): e202110938, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34791775

RESUMO

Microbial infections have become a great threat to human health and one of the main risks arises from direct contact with the surfaces contaminated by pathogenic microbes. Herein, a kind of hexagonal column interpenetrated spheres (HCISs) are fabricated by non-covalent assembly of plant gallic acid with quaternary ammonium surfactants. Different from one-time burst release of conventional antimicrobial agents, the HCIS acts like a "antimicrobial molecular bank" and releases the antimicrobial ingredients in a multistage way, leading to long-lasting antimicrobial performance. Taking advantage of strong hydrophobicity and adhesion, HCISs are applicable to various substrates and endowed with anti-water washing property, thus showing high in vitro antimicrobial efficiency (>99 %) even after being used for 10 cycles. Meanwhile, HCISs exhibit broad-spectrum antimicrobial activity against bacteria and fungi, and have good biocompatibility with mammalian cells. Such a low-cost and portable long-lasting antimicrobial agent meets the growing anti-infection demand in public spaces.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Materiais Biocompatíveis/farmacologia , Polifenóis/farmacologia , Tensoativos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Candida albicans/efeitos dos fármacos , Cátions/química , Cátions/farmacologia , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Tamanho da Partícula , Polifenóis/química , Staphylococcus aureus/efeitos dos fármacos , Tensoativos/química
7.
Soft Matter ; 17(44): 10080-10089, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34714904

RESUMO

The hydration of amino acids closely correlates the hydration of peptides and proteins and is critical to their biological functions. However, complete and quantitative understanding about the hydration of amino acids is lacking. Here, tightly and loosely bound water of 20 zwitterionic amino acids are quantitatively distinguished and determined by Raman spectroscopy with multivariate curve resolution (Raman-MCR) and differential scanning calorimetry (DSC). The total hydration water obtained from Raman-MCR and the tightly bound water determined by DSC have certain relevance, but they do not exactly correspond. In particular, Pro, Arg and Lys exhibit larger number of tightly bound water molecules (4.02-6.59), showing a significant influence on the onset transition temperature and the melting enthalpy values of water molecules, which provides direct evidence for their unique functions associated with biological water. Asn, Ser, Thr, Met, His and Glu have a smaller number of tightly bound water molecules (0.30-1.31), whilst the other remaining 11 amino acids only contain loosely bound water molecules. Four exceptional amino acids Ile, Leu, Phe and Val show fewer tightly bound water molecules but a higher number of loosely bound water molecules. As for the hydration shell structure, most amino acids except Pro and Trp enhance tetrahedral water structure and H-bonds relative to pure water and at least 1.9% of the hydration water molecules associated with the amino acids show non-hydrogen-bonded OH defects. This work combines two effective experimental techniques to reveal the hydration water structure and quantitatively analyze two kinds of bound water molecules of 20 amino acids.


Assuntos
Aminoácidos , Água , Sequência de Aminoácidos , Fragmentos de Peptídeos , Tripsina
8.
Biomed Res Int ; 2021: 5553486, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33997006

RESUMO

INTRODUCTION: Microribonucleic acids (miRNAs) have short (approximately 18 to 25) nucleotides and are evolutionarily conserved and endogenously expressed RNAs belonging to a family of noncoding RNA molecules. miRNA-373 regulates cell proliferation, migration, apoptosis, invasion, and repairing damaged DNA after hypoxia stress. Neonatal hypoxic-ischemic encephalopathy (HIE) refers to perinatal asphyxia caused by partial or complete hypoxia, reduced or suspended cerebral blood flow, and fetal or neonatal brain damage. We aim to investigate the relationship between miRNA-373 and HIF-1α, between miRNA-373 MMP-9, and between miRNA-373 VEGF in the occurrence and development of HIE. METHODS: Human (children) samples were divided into four groups (n = 15 in each group) according to HIE severity. The patient group was divided into middle, moderate, and severe HIE groups. The control group included healthy children or children with nonneurological diseases. The expressions of miRNA-373, HIF-1α, MMP-9, and VEGF were assayed in the serum samples. RESULTS: Our study showed a strong relationship between miRNA-373 and HIF-1α, between miRNA-373 and MMP-9, and between miRNA-373 and VEGF. The expression levels of miRNA-373, HIF-1α, MMP-9, and VEGF in the HIE groups were much higher than those of the control group. CONCLUSION: The increased change in miRNA-373 expression has a certain diagnostic significance on neonatal HIE. In the occurrence and development of HIE, miRNA-373 is positively correlated with HIF-1α, MMP-9, and VEGF.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia-Isquemia Encefálica , Doenças do Recém-Nascido , Metaloproteinase 9 da Matriz/metabolismo , MicroRNAs/metabolismo , Biologia Computacional , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/sangue , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Hipóxia-Isquemia Encefálica/genética , Hipóxia-Isquemia Encefálica/metabolismo , Hipóxia-Isquemia Encefálica/fisiopatologia , Recém-Nascido , Doenças do Recém-Nascido/genética , Doenças do Recém-Nascido/metabolismo , Doenças do Recém-Nascido/fisiopatologia , Metaloproteinase 9 da Matriz/sangue , Metaloproteinase 9 da Matriz/genética , MicroRNAs/sangue , MicroRNAs/genética , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
9.
J Phys Chem Lett ; 11(17): 7429-7437, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32803982

RESUMO

Hydration states of many self-assemblies directly relate to their structures and functions. Here, we use Raman multivariate curve resolution (Raman-MCR) assisted by differential scanning calorimetry and nuclear magnetic resonance to explore the hydration properties of aggregates formed by three cationic ammonium surfactants, trimethylene-1,3-bis(dodecyldimethylammonium bromide) (12-3-12(Br)2), didodecyldimethylammonium bromide (DDAB), and dodecyltrimethylammonium bromide (DTAB). For 12-3-12(Br)2, the transitions from spherical to rodlike and wormlike micelles lead to about 20% and 60% dehydration and gradually weaken water tetrahedral order and H-bond in hydration shells for both headgroup and hydrophobic chain. As to DDAB, unilamellar vesicles contain two kinds of hydration water species, but multicompartment vesicles exhibit decreased water order and weaker H-bond. DTAB only forms spherical micelles and its hydration structure is similar to that of the 12-3-12(Br)2 spherical micelles. This work provides a basis to explore the hydration states of complex biological self-assemblies.

10.
Int J Mol Sci ; 21(9)2020 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-32357554

RESUMO

As non-viral transgenic vectors, the piggyBac transposon system represents an attractive tool for gene delivery to achieve a long-term gene expression in immunotherapy applications due to its large cargo capacity, its lack of a trace of transposon and of genotoxic potential, and its highly engineered structure. However, further improvements in transpose activity are required for industrialization and clinical applications. Herein, we established a one-plasmid effective screening system and a two-step high-throughput screening process in yeast to isolate hyperactive mutants for mammalian cell applications. By applying this screening system, 15 hyperactive piggyBac transposases that exhibited higher transpose activity compared with optimized hyPBase in yeast and four mutants that showed higher transpose activity in mammalian cells were selected among 3000 hyPBase mutants. The most hyperactive transposase, bz-hyPBase, with four mutation sites showed an ability to yield high-efficiency editing in Chinese hamster ovarian carcinoma (CHO) cells and T cells, indicating that they could be expanded for gene therapy approaches. Finally, we tested the potential of this screening system in other versions of piggyBac transposase.


Assuntos
Plasmídeos/genética , Saccharomyces cerevisiae/enzimologia , Transposases/genética , Animais , Células CHO , Cricetulus , Elementos de DNA Transponíveis , Edição de Genes , Ensaios de Triagem em Larga Escala , Mutação , Saccharomyces cerevisiae/genética , Transposases/metabolismo
11.
ACS Appl Mater Interfaces ; 12(15): 17220-17229, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32193931

RESUMO

To address the challenge from microbial resistance and biofilm, this work develops three gemini peptide amphiphiles with basic tetrapeptide spacers 12-(Arg)4-12, 12-(Lys)4-12, and 12-(His)4-12 and finds that they exhibit varied antimicrobial/antibiofilm activities. 12-(Arg)4-12 shows the best performance, possessing the broad-spectrum antimicrobial activity and excellent antibiofilm capacity. The antimicrobial and antibiofilm activities strongly depend on the membrane permeation and self-assembling structure of these peptide amphiphiles. Gemini peptide amphiphile with highly polar arginine as the spacer, 12-(Arg)4-12, self-assembles into short rods that are prone to dissociate into monomers for permeating and lysing membrane , leading to its broad-spectrum antimicrobial activity and high efficiency in eradicating biofilm. Long rods formed by relatively weaker polar 12-(Lys)4-12 are less prone to disassemble into monomers for further membrane permeation, which makes it selectively kill more negatively charged bacteria and endow it medium antibiofilm activity. Low polar 12-(His)4-12 aggregates into long fibers, which are very difficult to dissociate and they mainly electrostatically bind on the negative microbial surface, resulting in its weakest antimicrobial and antibiofilm activity. This study reveals the effect of the antimicrobial peptide structure and aggregation on the antimicrobial activities and would be helpful for developing high-efficient antimicrobial peptides with antibiofilm activity.


Assuntos
Anti-Infecciosos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Biofilmes/efeitos dos fármacos , Anti-Infecciosos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Candida albicans/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Testes de Sensibilidade Microbiana , Microscopia Confocal , Oligopeptídeos/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia
12.
Soft Matter ; 15(46): 9458-9467, 2019 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-31742300

RESUMO

Peptide surfactants have shown many potential applications in biology and medicine; however, the mechanism of their interactions with biomembranes is still unclear. This work has studied the interactions of cationic peptide gemini surfactants based on lysine spacers (12-(Lys)n-12, n = 2, 4, and 6) with model biological membranes, which are represented by the vesicles separately formed by zwitterionic unsaturated phospholipid 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), anionic unsaturated phospholipid 1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DOPG, sodium salt) and the DOPC/DOPG (1 : 1) mixture. The experiment results show that the presence of negatively charged DOPG slightly affects the interaction manners of 12-(Lys)n-12 with the vesicles, while the interaction of 12-(Lys)2-12 with the phospholipid vesicles is significantly different from that of 12-(Lys)4-12 and 12-(Lys)6-12 with the vesicles. The binding strength decreases in the order of 12-(Lys)4-12 > 12-(Lys)6-12 > 12-(Lys)2-12. The 12-(Lys)4-12 surfactant solubilizes the DOPC vesicles, and makes the DOPC molecules join the surfactant stiff fibers and changes them into long and flexible wormlike micelles, while the 12-(Lys)6-12 and 12-(Lys)2-12 aggregates are disassembled by the DOPC vesicles, and the surfactant molecules join the DOPC vesicles and convert the unilamellar vesicles into multilamellar vesicles. This work should be helpful in understanding the interaction of peptide surfactants with phospholipid membranes.


Assuntos
Lipossomos/química , Lisina/química , Fosfolipídeos/química , Tensoativos/química , Peptídeos/química , Ligação Proteica , Conformação Proteica
13.
ACS Appl Mater Interfaces ; 11(18): 16357-16366, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-30991000

RESUMO

The use of smart drug carriers to realize cancer-targeted drug delivery is a promising method to improve the efficiency of chemotherapy and reduce its side effects. A surfactant-like peptide, Nap-FFGPLGLARKRK, was elaborately designed for cancer-targeted drug delivery based on an enzyme-triggered morphological transition of the self-assembled nanostructures. The peptide has three functional motifs: the aromatic motif of Nap-FF- to promote peptide self-assembly, the enzyme-cleavable segment of -GPLGLA- to introduce enzyme sensitivity, and the positively charged -RKRK- segment to balance the molecular amphiphilicity as well as to facilitate interaction with cell membranes. The peptide self-assembles into long fibrils with hydrophobic inner cores, which can encapsulate a high amount of anticancer drug doxorubicin (DOX). By having enzyme responsibility, these fibrils can be degraded into thinner ones by the cancer-overexpressed matrix metalloproteinase-7 (MMP7) at tumor sites and precipitate out to give sustained release of DOX, resulting in cancer-targeted drug delivery and selective cancer killing. In vivo antitumor experiments with mice confirm the high efficiency of such enzyme-responsive peptidic drug carriers in successfully suppressing the tumor growth and metastasis while greatly reducing the side effects. The study demonstrates the feasibility of using enzyme-sensitive peptide nanostructures for efficient and targeted drug delivery, which have great potential in biomedical cancer treatment.


Assuntos
Sistemas de Liberação de Medicamentos , Nanoestruturas/administração & dosagem , Neoplasias/tratamento farmacológico , Peptídeos/administração & dosagem , Células A549 , Animais , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Metaloproteinase 7 da Matriz/genética , Camundongos , Nanoestruturas/química , Neoplasias/patologia , Peptídeos/química , Tensoativos/administração & dosagem , Tensoativos/química , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Langmuir ; 35(18): 6154-6160, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-30983363

RESUMO

Peptide amphiphiles (PAs) can self-assemble into a variety of supramolecular structures with excellent biofunctions. However, their assembly with time has rarely been observed and reported. Here, we find that a novel gemini-type PA [12-(Lys)2-12], taking two lysine (Lys) groups as the spacer, shows an obvious assembly and evolution process with time. Driven by the strong hydrophobic interaction between the alkyl chains as well as the electrostatic force and hydrogen bonding among the peptide spacers, the 12-(Lys)2-12 molecules first self-assemble into vesicles and then transform into fibrils, ribbons, and belts with time. If replacing the -(Lys)2- spacer with four lysine groups [-(Lys)4-] or two glutamic acid groups [-(Glu)2-], the PA molecules do not show the aggregate growth with time. This indicates that the lysine structure and its length are important structural factors contributing to the dynamic aggregate evolution behavior. More interestingly, this assembly and evolution behavior is highly dependent on 12-(Lys)2-12 concentration. Only in the proper concentration region (0.5-0.7 mM), the self-assembly displays the aggregate growth with time. At lower or higher concentrations, the aggregate growth is largely delayed or inhibited. Moreover, we also find that the aggregate growth of 12-(Lys)2-12 is related to the fibril solubilization temperature ( Tf→s). The faster aggregate growth occurs when the temperature is much lower than Tf→s. This work gains new insights into the evolution of the self-assembling structures of peptide amphiphiles.


Assuntos
Lisina/química , Peptídeos/química , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular
15.
Langmuir ; 35(6): 2334-2342, 2019 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-30636427

RESUMO

Direct exposure or intake of engineered nanoparticles (ENPs) to the human body will trigger a series of complicated biological consequences. Especially, ENPs could either up- or downregulate peptide fibrillation, which is associated with various degenerative diseases like Alzheimer's and Parkinson's diseases. This work reports the effects of gold nanoparticles (AuNPs) with different shapes on the aggregation of an amyloid-ß peptide (Aß(1-40)) involved in Alzheimer's disease. Two kinds of AuNPs were investigated, i.e., gold nanospheres (AuNSs, ∼20 nm in diameter) and gold nanocubes (AuNCs, ∼20 nm in edge length). It was found that AuNPs play a catalytic role in peptide nucleation through interfacial adsorption of Aß(1-40). AuNSs with hybrid facets have higher affinity to Aß(1-40) because of the higher degree of surface atomic unsaturation than the {100}-faceted AuNCs. Therefore, AuNSs exert a more significant acceleration effect on the fibrillation process of Aß(1-40) than AuNCs. Besides, a shape-dependent secondary structure transformation of Aß(1-40) with different AuNPs was observed using Fourier transform infrared spectroscopy. The variation of peptide-NP and peptide-peptide interactions caused by the shape alteration of AuNPs influences the equilibrium of inter- and intramolecular hydrogen bonds, which is believed to be responsible for the shape-dependent secondary structure transformation. The study offers further understanding on the complicated NP-mediated Aß aggregation and also facilitates further development on designing and synthesizing task-specific AuNPs for amyloid disease diagnosis and therapy.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Nanopartículas Metálicas/química , Fragmentos de Peptídeos/metabolismo , Adsorção , Peptídeos beta-Amiloides/química , Ouro/química , Fragmentos de Peptídeos/química , Conformação Proteica em alfa-Hélice/efeitos dos fármacos , Conformação Proteica em Folha beta/efeitos dos fármacos , Multimerização Proteica/efeitos dos fármacos
16.
ACS Appl Bio Mater ; 2(1): 447-453, 2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-35016308

RESUMO

Bacterial resistance has caused a global healthcare emergency due to the buildup of antibiotics in the environment. Novel approaches that enable highly efficient bactericide and auto inactivation are highly desired. Past researches mainly focused on the on-off bactericidal ability of antibiotics, which often displays unsatisfactory bactericidal efficiency. Herein, we report a Trojan antibiotic that considers the affinity of antibiotics to bacteria. A disguised host-guest supramolecule based on cucurbituril (CB[7]) and a bola-type azobenzene compound with glycosylamine heads at both ends is synthesized. This supramolecule has a surface fully decorated with sugar-like components, which are highly analogous to wall components of bacteria. This Trojan antibiotic is benign to a wide spectrum of bacteria at a weak basic pH of approximately 9.0 under daylight conditions. However, this antibiotic becomes a potent bactericide toward both Gram-negative and Gram-positive bacteria at pH 4.0 under 365 nm UV irradiation. The dual use of pH and UV light greatly enhances the efficiency of the bactericidal effect so that the 50% minimum inhibitory concentration (MIC50) of the Trojan antibiotic is at least 10 times smaller than that of conventional drugs, and the removal of the UV source and reversal of pH automatically stop the antibacterial behavior, which prevents the buildup of active antimicrobial materials in the environment. We expect that the presented Trojan supramolecular strategy may open up a new paradigm in the fight against bacterial resistance.

17.
J Mater Chem B ; 7(9): 1435-1441, 2019 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-32255014

RESUMO

A water-soluble two-dimensional supramolecular organic framework (2D SOF) was prepared via self-assembly of cucurbit[8]uril (CB[8]) and a three-arm flat linker molecule, which contains a benzene ring as the core and three Brooker's merocyanine (BM) analogs as arms. The strong host-guest interactions between BM and CB[8] and the directional head-to-tail stacking modes between the BM arms synergistically led to the formation of a 2D SOF. The structure of the 2D SOF was verified by 1H NMR, 2D 1H NMR NOESY, and DLS characterizations, while the monolayer structure was characterized by Cryo-TEM and AFM measurements. The 2D SOF exhibited an obvious AIE enhancement effect in H2O. In addition, DNA induced photoluminescence enhancement was observed for the monomer. As a result, this AIEgen-based 2D SOF could feature not only as a cell visualizer but also as a tracker for the nucleus in biological imaging due to the dynamic assembly process.


Assuntos
DNA/química , Substâncias Macromoleculares/química , Microscopia Confocal/métodos , Benzopiranos/química , Hidrocarbonetos Aromáticos com Pontes/química , Microscopia Crioeletrônica , DNA/metabolismo , Células HeLa , Humanos , Imidazóis/química , Indóis/química , Substâncias Macromoleculares/metabolismo , Microscopia de Força Atômica , Água/química
18.
ACS Appl Mater Interfaces ; 11(3): 2790-2801, 2019 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-30588791

RESUMO

The development of bacterial resistant strains is a global health concern. Designing antibiotics that limit the rise of pathogenic resistance is essential to efficiently treat pathogenic infections. Self-assembling amphiphilic molecules are an intriguing platform for the treatment of pathogens because of their ability to disrupt bacterial membranes and function as drug nanocarriers. We have designed cationic peptide amphiphiles (PAs) that can form micelles, nanofibers, and twisted ribbons with the aim of understanding antimicrobial activity at the supramolecular level. We have found that micelle-forming PAs possess excellent antimicrobial activity against various Gram-positive and Gram-negative pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Klebsiella pneumoniae with minimal inhibitory concentrations (MICs) ranging between 1 and 8 µg/mL, when compared to nanofibers with MICs >32 µg/mL. The data suggest that the antimicrobial activity of the PAs depends on their morphology, amino acid sequence, the length of the alkyl tail, and the overall hydrophobicity of the PA. Scanning electron microscopy, confocal microscopy, and flow cytometry studies using MRSA and Escherichia coli K12 strains showed that PAs increase cell membrane permeability and disrupt the integrity of pathogen's membrane, leading to cell lysis and death. PAs are a promising platform to develop new antimicrobials that could work as nanocarriers to develop synergistic antibacterial therapies.


Assuntos
Antibacterianos/administração & dosagem , Peptídeos Catiônicos Antimicrobianos/química , Infecções Bacterianas/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Antibacterianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/patologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/patogenicidade , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/patogenicidade , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Microscopia Eletrônica de Varredura , Nanofibras/química , Nanoestruturas/química
19.
Langmuir ; 34(45): 13652-13661, 2018 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-30350992

RESUMO

Understanding the interactions of amphiphile molecules with biological membranes is very important to many practical applications. Amino acid amphiphiles are a kind of mild surfactants and have many unique performances. However, their interactions with phospholipid membranes have scarcely been studied. This work has studied the interactions of glutamic acid-based gemini amphiphile C12(Glu)2C12 and single-chain amphiphile C12Glu with the model biomembrane formed by the phospholipid 1,2-dioleoyl- sn-glycero-3-phosphocholine (DOPC). The partition coefficients of C12(Glu)2C12 and C12Glu into the DOPC vesicles were derived from the observed enthalpy curves obtained by isothermal titration calorimetry at temperatures of 25.0 and 37.0 °C, and pHs of 5.6 and 7.4, corresponding to the skin surface and human physiological conditions. The results from cryogenic transmission electron microscopy, dynamic light scattering, and zeta potential measurements show that the amphiphile molecules form different aggregates, which make the amphiphile molecules exhibit different partition abilities to the DOPC vesicles. For C12Glu, the molecules form shorter wormlike micelles with a lower surface charge at all the pHs and temperatures used, and the partition coefficient of C12Glu into the DOPC vesicles does not change with temperature and pH. Differently, the C12(Glu)2C12 molecules form fibers with a larger negative charge and belts with a smaller negative charge at pHs 7.4 and 5.6, respectively, no matter what temperature is used. As a result, the partitions of C12(Glu)2C12 into the DOPC vesicles are markedly different at these two pH values, and the belts at pH 7.4 exhibit a stronger partition ability than the fibrils at pH 5.6. Moreover, at any temperature and pH, C12(Glu)2C12 shows a stronger partition ability than C12Glu. This work can help to understand the relationship between the molecular structure and aggregate structure of amino acid amphiphiles and their partition abilities into the biomembranes.


Assuntos
Glutamatos/química , Bicamadas Lipídicas/química , Fosfatidilcolinas/química , Tensoativos/química , Concentração de Íons de Hidrogênio , Micelas , Estrutura Molecular , Temperatura , Termodinâmica
20.
ACS Appl Mater Interfaces ; 10(29): 24349-24360, 2018 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-29979028

RESUMO

A series of surfactant-like peptides have been designed for inducing DNA condensation, which are all comprised of the same set of amino acids in different sequences. Results from experiments and molecular dynamics simulations show that the peptide's self-assembly and DNA-interaction behaviors can be well manipulated through sequence variation. With optimized pairing modes between the ß-sheets, the peptide of I3V3A3G3K3 can induce efficient DNA condensation into virus-mimicking structures. The condensation involves two steps; the peptide molecules first bind onto the DNA chain through electrostatic interactions and then self-associate into ß-sheets under hydrophobic interactions and hydrogen bonding. In such condensates, the peptide ß-sheets act as scaffolds to assist the ordered arrangement of DNA, mimicking the very nature of the virus capsid in helping DNA packaging. Such a hierarchy affords an extremely stable structure to attain the highly condensed state and protect DNA against enzymatic degradation. Moreover, the condensate size can be well tuned by the DNA length. The condensates with smaller sizes and narrow size distribution can deliver DNA efficiently into cells. The study helps not only for probing into the DNA packaging mechanism in virus but also delineating the role of peptide self-assembly in DNA condensation, which may lead to development of peptide-based gene vectors for therapeutic applications.


Assuntos
Nanoestruturas , DNA , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Peptídeos , Estrutura Secundária de Proteína
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