TOXICON
·
2013
·
IF 2.924
Ying Zhang,Li Zhong,Bin Zhou,Jin-yu Chen,Chun-mei Li
To more fully understand the mechanism by which persimmon tannin (PT) inhibited phospholipase A 2 (PLA 2 ) and the structural requirements of PT for the inhibition, the interactions between PLA 2 and seven characteristic structural elements of PT including epigallocatechin-3-gallate (EGCG), myricetin, epicatechin-3-gallate (ECG), epicatechin-3-gallate-(4β → 8, 2β → O → 7)-epicatechin-3-gallate (A-type ECG dimer), epigallocatechin-3-gallate-(4β → 8, 2β → O → 7)-epigallocatechin-3-gallate (A-type EGCG dimer), epicatechin-(4β → 8, 2β → O → 7)-epicatechin (A-type EC dimer) and epicatechin-(4β → 8)-epicatechin (B-type EC dimer) were studied by enzymatic and spectroscopic methods. Molecular docking was also used to explore the possible residues involved in the interactions. The results revealed that A-type EGCG dimer and A-type ECG dimer showed higher inhibitory effects on the catalytic activity of PLA 2 than monomers and B-type dimer. They induced greater conformational changes in PLA 2 than other structural elements. In addition, molecular docking studies revealed that expect for lysine residues, other residues such as Trp18, Try27, Gly29, His47 and Tyr63 were involved in the interactions. We propose that A-type EGCG and ECG dimer units may be structural requirements for the interaction between PT and PLA 2 . Our data provide an additional structural basis for anti-PLA 2 activity of persimmon tannin.
研究领域:
生物化学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2019
·Vol. 20
·期 8
·1961
·
IF 4.183
Bing Yu,Qingye Meng,Hao Hu,Tao Xu,Youqing Shen,Hailin Cong
Polymeric micelles (PMs) have been applied widely to transport hydrophobic drugs to tumor sites for cancer treatment. However, the low load efficiency of the drug in the PMs significantly reduces the therapeutic efficiency. We report here that disulfide-linked camptothecin (CPT) as a kind of dimeric drug can be effectively embedded in the core of poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) (PCL–PEG–PCL) PMs for improving drug-loading efficiency, and PEG can be used as a hydrophilic shell. Moreover, the dimeric CPT-loaded PCL–PEG–PCL PMs exhibited excellent solubility in phosphate-buffered saline (PBS) media and significant cytotoxicity to cancer cells.Keywords:dimeric drug;camptothecin;micelles;cancer therapy
研究领域:
药学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LIQUID CRYSTALS
·
2024
·
IF 2.4
Xin Zhang,Deyuan Yao,Xiaomei Pan,Erqiao Xue,Peng Cheng,Tingting Ye,Junfeng Ding
The crystal structures of liquid crystals, particularly various oligomers, have garnered significant attention, laying the groundwork for developing new materials and devices. Here, we demonstrate pressure plays a crucial role in the structure of liquid crystals. High-pressure Raman and photoluminescence spectra were on 5CB (4-cyano-4’−pentylbiphenyl) liquid crystal. Upon compression, the appearance of prominent fluorescence peaks suggests a phase transition. The Raman peaks, reflecting the C–H and C≡N bonds, exhibit splitting at a pressure of 3.2 GPa, further confirming the pressure-induced phase transition. The splitting is consistent with earlier calculations on the stretching vibration of the C≡N bond for various oligomers and indicates a phase transition from monomers to dimers in 5CB liquid crystal. The opposite shifts in Raman modes under pressure, specifically the blue-shift of C–H bonds and the red-shift of C≡N bonds, indicate that pressure enhances intermolecular interactions and leads to conjugation between the electrons on the C≡N bonds and the C–H bonds, resulting in dimer formation. Our findings not only reveal a novel strategy for producing oligomers in liquid crystals through the application of high pressure but also highlight that Raman spectroscopy is a valid, non-contact method for investigating the mechanisms of oligomerization.
研究领域:
材料科学
·
物理化学
✓ 已验证
DOI
高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
·
2022
·Vol. 40
·期 6
·584-592
·
IF 3.815
Xiao Yang,He Chong,Yang Zi-Fan,Chen Er-Qiang,Lu Huan-Jun,Li Xiao-Hong,Tu Ying-Feng
We demonstrate here a novel method for the design of liquid crystals (LCs) via the cyclization of mesogens by flexible chains. For two azobenzene-4,4′-dicarboxylate derivatives, the cyclic dimer, cyclic bis(tetraethylene glycol azobenzene-4,4′-dicarboxylate) (CBTAD), shows LC properties with smectic A phase, while its linear counterpart, bis(2-(2′-hydroxyethyloxy)ethyl azobenzene-4,4′-dicarboxylate (BHAD), has no LC phase. The difference is ascribed to the shackling effect from the cyclic topology, which leads to the much smaller entropy change during phase transitions and increases the isotropic temperature greatly for cyclics. In addition, the trans -to- cis isomerization of azobenzene groups under UV-light is also limited in CBTAD. With the reversible isomerization of azobenzene groups, CBTAD showed interesting isothermal phase transition behaviors, where the LC phase disappeared upon photoirradiation of 365 nm UV-light, and recovered when the UV-light was off. Combined with the smectic LC nature, a novel UV-light tuned visible light regulator was designed, by simply placing CBTAD in two glass plates. The scattered phase of smectic LC was utilized as the “OFF” state for light passage, while the UV-light induced isotropic phase was utilized as the “ON” state. The shackling effect outlined here should be applicable for the design of cyclic LC oligomers/polymers with special properties.
研究领域:
材料科学
·
化学
✓ 已验证
DOI
高影响因子
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
·
2025
·Vol. 122
·期 13
·e2426006122
·
IF 9.1
Fengwei Li,Mengmeng Zhang,Chao Liu,Jie Cheng,Yawen Yang,Xiangda Peng,Zhifeng Li,Wenfeng Cai,Haipeng Yu,Junjie Wu,Yuyu Guo,Hongkun Geng,Yun Fa,Youming Zhang,Dalei Wu,Yizhen Yin
Macrocyclic peptides have emerged as promising drug candidates, filling the gap between small molecules and large biomolecules in drug discovery. The antiapoptotic protein myeloid cell leukemia 1 (MCL1) is crucial for numerous cancers, yet it presents challenges for selective targeting by traditional inhibitors. In this study, we identified a macrocyclic peptide, 5L1, that strongly binds to MCL1, with a dissociation constant (KD) of 7.1 nM. This peptide shows the potential to specifically inhibit the function of MCL1, and demonstrates effective antitumor activity against several blood tumor cell lines with the half maximal inhibitory concentration (IC50) values for cell-penetrating peptide-conjugated 5L1 in the range of 0.6 to 3 μM. Structural analysis revealed that it functions similarly to molecular glue, capable of binding to two MCL1 molecules simultaneously and inducing their homodimerization. This unique mechanism of action distinguishes it from traditional small-molecule MCL1 inhibitors, underscoring the potential of macrocyclic peptides functioning as molecular glues. Moreover, it inspires the development of highly selective inhibitors targeting MCL1 and other related targets with this glue-like mechanism.
研究领域:
药物化学
·
癌症生物学
·
结构生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CROP PROTECTION
·
2020
·
IF 2.381
Guanglong Ding,Jingyue Tang,Wenbing Zhang,Yanran Li,Junfan Niu,Weichen Wang,Hong Huo,Jianqiang Li,Yongsong Cao
Auxinic herbicides are widely used to control broadleaf weeds in cereal crop fields due to their excellent herbicidal activities. However, volatile drifting caused by their high vapor pressures is a great threat to neighbouring susceptible crops and environment and severely limits auxinic herbicide applications. In this study, a series of auxinic herbicide dimers were synthesized using 2,4-D, dicamba and MCPA as monomers to reduce their vapor pressures. The results showed that all of the dimers significantly reduced volatilities due to larger molecular weight. The dimers linked with two ester bonds had 2-fold higher herbicidal efficacies than their corresponding monomers in filed experiments. The dimers linked with amide bonds appeared to function as contact action and systemic action herbicides. The dimers, 3a-2(ethane-1,2-diylbis (2-(2,4-dichlorophenoxy)acetate)), 3a-4(2-((2-(2,4-dichlorophenoxy)acetyl)thio)ethyl 2-(2,4-dichlorophenoxy)acetate), 3b-2(ethane-1,2-diylbis(2-(4-chloro-2-methylphenoxy)acetate)) and 3c-2(ethane-1,2-diylbis(3,6-dichloro-2-methoxybenzoate)) significantly increased the efficacies and reduced volatilities, thus could be developed as potential novel postemergence herbicides.
研究领域:
植物学
·
农业科学
✓ 已验证
产品关联
DOI
高影响因子
Pharmaceutics
·
2023
·Vol. 15
·期 7
·1874
·
IF 5.4
Heming Zhao,Liming Gong,Hao Wu,Chao Liu,Yanhong Liu,Congcong Xiao,Chenfei Liu,Liqing Chen,Mingji Jin,Zhonggao Gao,Youyan Guan,Wei Huang
Prostate cancer (PC) is one of the common malignant tumors of the male genitourinary system. Here, we constructed PTX@ZIF-8, which is a metal-organic-framework-encapsulated drug delivery nanoparticle with paclitaxel (PTX) as a model drug, and further modified the synthesized peptide dimer (Di-PEG2000-COOH) onto the surface of PTX@ZIF-8 to prepare a nanotargeted drug delivery system (Di-PEG@PTX@ZIF-8) for the treatment of prostate cancer. This study investigated the morphology, particle size distribution, zeta potential, drug loading, encapsulation rate, stability, in vitro release behavior, and cytotoxicity of this targeted drug delivery system, and explored the uptake of Di-PEG@PTX@ZIF-8 by human prostate cancer Lncap cells at the in vitro cellular level, as well as the proliferation inhibition and promotion of apoptosis of Lncap cells by the composite nanoparticles. The results suggest that Di-PEG@PTX@ZIF-8, as a zeolitic imidazolate frameworks-8-loaded paclitaxel nanoparticle, has promising potential for the treatment of prostate cancer, which may provide a novel strategy for the delivery system targeting prostate cancer.Keywords:metal-organic framework;paclitaxel;peptide dimer;prostate cancer
研究领域:
药学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2021
·
IF 5.89
Yu Shimin,Sun Zhongqi,Zhang Zhanxiang,Sun Haoran,Liu Lina,Wang Wuyi,Li Mu,Zhao Qingsong,Li Tianlong
With the development of designed materials and structures, a wide array of micro/nanomachines with versatile functionalities are employed for specific sensing applications. Here, we demonstrated a magnetic propelled microdimer-based point-of-care testing system, which can be used to provide the real-time data of plasma glucose and lipids relying on the motion feedback of mechanical properties. On-demand and programmable speed and direction of the microdimers can be achieved with the judicious adjustment of the external magnetic field, while their velocity and instantaneous postures provide estimation of glucose, cholesterol, and triglycerides concentrations with high temporal accuracy. Numerical simulations reveal the relationship between motility performance and surrounding liquid properties. Such technology presents a point-of-care testing (POCT) approach to adapt to biofluid measurement, which advances the development of microrobotic system in biomedical fields.
研究领域:
生物医学工程
·
材料科学
·
诊断学
✓ 已验证
DOI
高影响因子
CHEMICAL PHYSICS
·
2019
·
IF 1.822
Pengfei Wang,Liyuan Liu,Xiangchao Wang,Jianbing Zhang,Wei Qi,Hongwei Zhao,Zhen Tian,Mingxia He
A silicon-based sensor, consisting of periodical split ring resonators was demonstrated to monitor monomeric and dimeric insulin solutions in terahertz time-domain spectroscopy (THz-TDS). As concentration increases, the resonant frequencies of sensor show red shifts with a rapid trend in dilute solutions and a slow trend in concentrated solutions, consistent with CST simulations. For monomeric insulin, the turning concentration is 11.6 mg/ml and the total frequency shift is larger than that of dimeric insulin which shows a turning concentration at 17.4 mg/ml. The deviation in frequency shift and turning concentration can be attributed to the structural changes of insulin during dimerization process.
研究领域:
生物物理学
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
FUEL
·
2016
·
IF 3.611
Junbo Zhou,Yu Qiao,Wenxia Wang,Erwei Leng,Jingchun Huang,Yun Yu,Minghou Xu
This paper reports the formation of styrene monomer, dimer and trimer in the primary volatiles during fast pyrolysis of polystyrene in a wire-mesh reactor where secondary reactions of primary pyrolysis volatiles are minimized. Styrene monomer is the most abundant product in the primary volatiles from polystyrene pyrolysis, with a selectivity of 48–69 wt% depending on pyrolysis temperature, while dimer and trimer only have selectivities of 8–10 and 9–30 wt%, respectively. High temperature promotes the formation of styrene monomer and suppresses the formation of styrene trimer, but with little effect on the formation of styrene dimer. It is also found that the selectivities of styrene monomer, dimer and trimer show negligible changes with increasing the conversion level at the same pyrolysis temperature. The results suggest neither 1,3-hydrogen transfer nor intermolecular benzyl radical addition is the dominant formation mechanism for styrene dimer. The styrene dimer is more likely produced via the 1,7- and 7,3-hydrogen transfer mechanism.
研究领域:
化学工程
·
材料科学
·
能源科学
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2014
·
IF 3.432
Ke-Guang Cheng,Chun-Hua Su,Lin-Dong Yang,Jun Liu,Zhen-Feng Chen
Five dimeric oleanolic acids linked at C-28 by 1,6-hexanediamine, or built around the carbon chains of varying lengths between two carboxyl groups were synthesized, to investigate the effect of internal spacer length and species upon the stereochemical features and anti-tumor activity of the resultant bis-oleanolic acids. The IC 50 values of these dimeric compounds for cytotoxicity evaluation in vitro against Hep-G2, A549, BGC-823, MCF-7 and PC-3 tumor cell lines, were mainly under 10.0 μM. This result was much better than the inhibition of proliferation against tested tumor cell lines of the monomer oleanolic acid and the commercial anticancer drug 5-fluorouracil. The cytotoxicity selectivity detection revealed that dimer 11c exhibited low cytotoxicity towards normal human liver cell HL-7702. A combination of fluorescence staining observation and flow cytometric analysis indicated that 11c could induce Hep-G2 cell apoptosis . Molecular mechanism studies suggested that 11c induced apoptosis is mediated through the intrinsic apoptotic pathway with changes in mitochondrial membrane potential by finally activating effector caspase-3/9 to trigger cell apoptosis. Further studies revealed that 11c caused cell cycle arrest at G1 phase in Hep-G2 cells. Taken together, these results suggest that 11c may be a potential candidate for further cancer research.
研究领域:
药理学
·
肿瘤学
·
有机化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL PHYSICS
·
2021
·
IF 2.348
Zenan Zhao,Simin Cao,Haoyang Li,Dong Li,Yanping He,Xin Wang,Jinquan Chen,Sanjun Zhang,Jianhua Xu,Jay R. Knutson
Thiazole orange (TO), an asymmetric cyanine dye , has been widely used in biomolecular detection and imaging of DNA/ RNA in gels, due to its unique fluorogenic behavior: fluorescence of free dye in aqueous solution is very weak, but emission can be significantly enhanced in nucleic-acid-bound dye. Herein we describe the ultrafast excited-state dynamics of free TO in aqueous solution by exploiting both a femtosecond upconversion spectrophotofluorometer and a picosecond time-correlated single-photon counting (TCSPC) apparatus. For the first time, the fluorescence lifetime of TO monomer in water was found to be ∼1 ps, mixed with concurrent solvent relaxation (which was confirmed by the experimental results of TO in DMSO). Even at moderate TO concentration, this lifetime has an amplitude (a measure of molecular fraction) that significantly dominates other lifetimes, and this is the origin of weak steady state fluorescence of free TO in water. We also found a novel slower decay component around 34 ps. Interestingly and in addition, the lifetime component on the 30–40 ps timescale was also found in TO-γ-Cyclodextrin (CD) complexes. The fraction of this component increased with the addition of γ-CD. Cyclodextrin has been reported to promote the aggregation of TO. Thus, although a very coincidental match of this time constant by one for a torsional process within the cavity can not be ruled out, we ascribe the shared 30–40 ps component to the lifetime of a highly quenched TO dimer experiencing intra-and inter-molecular rearrangement.
研究领域:
生物物理学
·
光化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）