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51.
52.
Dr. Ma Su Dr. Yan Shi Minghui Wang Ruixuan Gao Jianfeng Wu Hai Xu Chuanwu Xi Prof. Jianfeng Cai 《ChemMedChem》2019,14(23):1963-1967
Host Defense Peptides (HDPs) have gained considerable interest due to the omnipresent threat of bacterial infection as a serious public health concern. However, development of HDPs is impeded by several drawbacks, such as poor selectivity, susceptibility to proteolytic degradation, low-to-moderate activity and requiring complex syntheses. Herein we report a class of lipo-linear α/urea-γ-AApeptides with a hybrid backbone and low molecular weight. The heterogeneous backbone not only enhances chemodiversity, but also shows effective antimicrobial activity against Gram-positive bacteria and is capable of disrupting bacterial membranes and killing bacteria rapidly. Given their low molecular weight and ease of access via facile synthesis, they could be practical antibiotic agents. 相似文献
53.
54.
Cuicui Ding Min Zhang Miao Ma Jiaojiao Zheng Qili Yang Ren Feng 《Polymer International》2019,68(8):1468-1477
Hydrogels with environment‐sensitive properties have great potential applications in the controlled drug release field. In this paper, hybrid hydrogels with semi‐interpenetrating polymer networks (semi‐IPNs), composed of poly(N‐isopropylacrylamide) (PNIPAM) as the thermo‐sensitive component by in situ polymerization and self‐assembled collagen nanofibrils as the pH‐sensitive framework, were prepared for controlled release of methyl violet as a model drug. From Fourier transform infrared spectroscopy and scanning electron microscopy, it was indicated that the crosslinking of PNIPAM in the presence of collagen nanofibrils led to the formation of semi‐IPNs with homogeneous porous structure, and the semi‐IPNs showed improved thermal stability and elastic properties compared with the native collagen as determined using differential scanning calorimetry and rheologic measurements. Furthermore, the semi‐IPNs possessed swelling behaviors quite different from those of neat collagen or PNIPAM hydrogel under various pH values and temperatures. Correspondingly, as expected, the drug release behavior in vitro for semi‐IPNs performed variously compared with that for single‐component semi‐IPNs, which revealed the tunable performance of semi‐IPNs for release ability. Finally the thermo‐ and pH‐responsive mechanism of the semi‐IPNs was illuminated to provide guidance for the application of the thermo‐ and pH‐sensitive collagen‐based hybrid hydrogels in controlled drug delivery systems. © 2019 Society of Chemical Industry 相似文献
55.
Shrikrishnan Sankaran Judith Becker Christoph Wittmann Arnzazu del Campo 《Small (Weinheim an der Bergstrasse, Germany)》2019,15(5)
On‐demand and long‐term delivery of drugs are common requirements in many therapeutic applications, not easy to be solved with available smart polymers for drug encapsulation. This work presents a fundamentally different concept to address such scenarios using a self‐replenishing and optogenetically controlled living material. It consists of a hydrogel containing an active endotoxin‐free Escherichia coli strain. The bacteria are metabolically and optogenetically engineered to secrete the antimicrobial and antitumoral drug deoxyviolacein in a light‐regulated manner. The permeable hydrogel matrix sustains a viable and functional bacterial population and permits diffusion and delivery of the synthesized drug to the surrounding medium at quantities regulated by light dose. Using a focused light beam, the site for synthesis and delivery of the drug can be freely defined. The living material is shown to maintain considerable levels of drug production and release for at least 42 days. These results prove the potential and flexibility that living materials containing engineered bacteria can offer for advanced therapeutic applications. 相似文献
56.
Histone deacetylase inhibitors (HDACIs) are responsible for controlling gene expression by modulating the acetylation status of histone proteins. Furthermore, they modulate the activity of cytoplasmic non-histone proteins. Due to the involvement of HDACs in neurodevelopment, memory formation, and cognitive processes, HDACIs have been suggested as innovative agents for the treatment of neurodegenerative disorders such as Alzheimer's disease (AD). Given their mechanisms of action and the complex nature of AD, HDACIs have been proposed for the design of novel multitarget ligands (MTLs). To this aim, the fragment responsible for HDAC inhibition has been coupled with other structures that are able to provide additional biological actions, such as antioxidant activity or the inhibition of phosphodiesterase 5, transglutaminase 2, and glycogen synthase kinase 3β. Herein we discuss recent efforts to design HDACI-based MTLs as potential disease-modifying entities. 相似文献
57.
为研究某圆柱形带壳推进剂装药的枪击响应特性,设计了一种12.7 mm子弹撞击试验。利用高速摄影机记录带壳装药在子弹撞击下的响应过程,并测试不同距离、方位处的空气超压及壳体破片速度,同时进行带壳装药在理想爆轰条件下的数值计算,得到了带壳装药的能量释放率。一共开展了四次圆柱形带壳装药的枪击试验,前三次装药发生了爆燃反应,第四次几乎无反应。结果表明:子弹撞击位置对圆柱形带壳装药的反应和能量释放率有较大影响,当子弹垂直入射带壳装药轴线后,推进剂发生点火、冒烟、熄火和低压燃烧的时序响应,其相对能量释放率为1.146%;而当子弹撞击位置偏离轴线一定距离时,推进剂几乎无反应,其相对能量释放率仅为0.473%;推进剂的反应对壳体破片有加速效应,带壳装药发生爆燃反应时的破片速度可达428.6 m·s~(-1),而几乎无反应时的最高破片速度仅有70.1 m·s~(-1)。 相似文献
58.
Dr. Eduarda Mendes Enrico Cadoni Filipa Carneiro Dr. Marta B. Afonso Hugo Brito Dr. João Lavrado Dr. Daniel J. V. A. dos Santos Dr. Jorge B. Vítor Prof. Stephen Neidle Prof. Cecília M. P. Rodrigues Prof. Alexandra Paulo 《ChemMedChem》2019,14(14):1325-1328
Quadruplex nucleic acids are promising targets for cancer therapy. In this study we used a fragment-based approach to create new flexible G-quadruplex (G4) DNA-interactive small molecules with good calculated oral drug-like properties, based on quinoline and triazole heterocycles. G4 melting temperature and polymerase chain reaction (PCR)-stop assays showed that two of these compounds are selective G4 ligands, as they were able to induce and stabilize G4s in a dose- and DNA sequence-dependent manner. Molecular docking studies have suggested plausible quadruplex binding to both the G-quartet and groove, with the quinoline module playing the major role. Compounds were screened for cytotoxicity against four cancer cell lines, where 4,4′-(4,4′-(1,3-phenylene)bis(1H-1,2,3-triazole-4,1-diyl))bis(1-methylquinolin-1-ium) ( 1 d ) showed the greater activity. Importantly, dose–response curves show that 1 d is cytotoxic in the human colon cancer HT-29 cell line enriched in cancer stem-like cells, a subpopulation of cells implicated in chemoresistance. Overall, this study identified a new small molecule as a promising lead for the development of drugs targeting G4 in cancer stem cells. 相似文献
59.
Dr. Johann Dion Fumi Minoshima Sayoko Saito Kayo Kiyoi Kayo Hasehira Dr. Hiroaki Tateno 《Chembiochem : a European journal of chemical biology》2019,20(12):1606-1611
Human pluripotent stem cells (hPSCs) are attractive resources for regenerative medicine, but medical applications are hindered by their tumorigenic potential. Previously, a hPSC-specific lectin probe, rBC2LCN, was identified through comprehensive glycome analysis by using high-density lectin microarrays. Herein, a lectin–doxorubicin (DOX) prodrug conjugate, with controllable photolysis activation for the elimination of tumorigenic human induced pluripotent stem cells, has been developed. rBC2LCN was fused with a biotin-binding protein, tamavidin (BC2Tama), and the fusion protein was expressed in Escherichia coli and purified by means of affinity chromatography. BC2Tama was then conjugated with doxorubicin-photocleavable biotin (DOXPCB). The BC2Tama–DOXPCB conjugates were observed to bind to hPSCs followed by internalization. Upon exposure to ultraviolet light, DOX was released inside the cells, which allowed specific killing of the hPSCs. Thus, BC2Tama–DOXPCB should be useful for the targeted elimination of hPSCs contained in hPSC-derived cell therapy products. This is the first report of the generation of lectin–prodrug conjugates. BC2Tama should be applicable for the targeted delivery of various types of biotinylated compounds into hPSCs. 相似文献
60.
Max J. Cotler Erin B. Rousseau Khalil B. Ramadi Joshua Fang Ann M. Graybiel Robert Langer Michael J. Cima 《Small (Weinheim an der Bergstrasse, Germany)》2019,15(37)
Enhanced understanding of neuropathologies has created a need for more advanced tools. Current neural implants result in extensive glial scarring and are not able to highly localize drug delivery due to their size. Smaller implants reduce surgical trauma and improve spatial resolution, but such a reduction requires improvements in device design to enable accurate and chronic implantation in subcortical structures. Flexible needle steering techniques offer improved control over implant placement, but often require complex closed‐loop control for accurate implantation. This study reports the development of steerable microinvasive neural implants (S‐MINIs) constructed from borosilicate capillaries (OD = 60 µm, ID = 20 µm) that do not require closed‐loop guidance or guide tubes. S‐MINIs reduce glial scarring 3.5‐fold compared to prior implants. Bevel steered needles are utilized for open‐loop targeting of deep‐brain structures. This study demonstrates a sinusoidal relationship between implant bevel angle and the trajectory radius of curvature both in vitro and ex vivo. This relationship allows for bevel‐tipped capillaries to be steered to a target with an average error of 0.23 mm ± 0.19 without closed‐loop control. Polished microcapillaries present a new microinvasive tool for chronic, predictable targeting of pathophysiological structures without the need for closed‐loop feedback and complex imaging. 相似文献