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排序方式: 共有1118条查询结果,搜索用时 10 毫秒
1.
Peroxisome proliferator-activated receptor α (PPARα) is an important regulator of hepatic lipid metabolism which functions through ligand binding. Despite high amino acid sequence identity (>90%), marked differences in PPARα ligand binding, activation and gene regulation have been noted across species. Similar to previous observations with synthetic agonists, we have recently reported differences in ligand affinities and extent of activation between human PPARα (hPPARα) and mouse PPARα (mPPARα) in response to long chain fatty acids (LCFA). The present study was aimed to determine if structural alterations could account for these differences. The binding of PPARα to LCFA was examined through in silico molecular modeling and docking simulations. Modeling suggested that variances at amino acid position 272 are likely to be responsible for differences in saturated LCFA binding to hPPARα and mPPARα. To confirm these results experimentally, LCFA binding, circular dichroism, and transactivation studies were performed using a F272I mutant form of mPPARα. Experimental data correlated with in silico docking simulations, further confirming the importance of amino acid 272 in LCFA binding. Although the driving force for evolution of species differences at this position are yet unidentified, this study enhances our understanding of ligand-induced regulation by PPARα and demonstrates the efficacy of molecular modeling and docking simulations. 相似文献
2.
使用密度泛函理论方法研究了量子点(CdSe)2与配体L(L=PH3、PH2Me、PHMe2、PMe3、NH3、NH2Me、NHMe2、NMe3)之间的相互作用及其产物的结构和性质。配体中的P或N原子与Cd原子上分别形成较强的Cd—P和Cd—N配位键,从而影响(CdSe)2的结构和电子性质。配体作用下,(CdSe)2的几何结构、电荷分布、轨道能级、吸收光谱等均发生变化,但2类配体的影响,尤其是甲基数目的影响,存在较大差异。 相似文献
3.
Dengue virus is a major issue of tropical and sub-tropical regions. Dengue virus has been the cause behind the major alarming epidemics in the history with mass causalities from the decades. Unavailability of on-shelf drugs for the prevention of further proliferation of virus inside the human body results in immense number of deaths each year. This issue necessitates the design of novel anti-dengue drug. The protease enzyme pathway is the critical target for drug design due to its significance in the replication, survival and other cellular activities of dengue virus. Therefore, approximately eighteen million compounds from the ZINC database have been virtually screened against nonstructural protein 3 (NS3). The incremental construction algorithm of Glide docking program has been used with its features high throughput virtual screening (HTVS), standard precision (SP), extra precision (XP) and in combination of Prime module, induced fit docking (IFD) approach has also been applied. Five top-ranked compounds were then selected from the IFD results with better predicted binding energies with the catalytic triad residues (His51, Asp75, and Ser135) that may act as potential inhibitors for the underlying target protease enzyme. The top-ranked compounds ZINC95518765, ZINC44921800, ZINC71917414, ZINC39500661, ZINC36681949 have shown the predicted binding energies of −7.55, −7.36, −8.04, −8.41, −9.18 kcal/mol, respectively, forming binding interactions with three catalytically important amino acids. Top-docking poses of compounds are then used in molecular dynamics (MD) simulations. In computational studies, our proposed compounds confirm promising results against all the four serotypes of dengue virus, strengthening the opportunity of these compounds to work as potential on-shelf drugs against dengue virus. Further experimentation on the proposed compounds can result in development of strong inhibitors. 相似文献
4.
合成了新的三配位体邻甲硫基-N-β-巯基乙酰苯胺(MTPMA),其结构经红外光谱(IR)、核磁共振(1HNMR)、质谱(MS(FAB+))和元素分析确认.用配体交换方法制备了两种混合配位体复合物99Tcm(L3,L1a)和99Tcm(L3,L1b).其中,L3为三配位体,L1a、L1b分别为单配位体乙硫醇和异丙硫醇.确定了这两种混配复合物的最佳标记条件,在此条件下,放射化学纯度(RCP )>90%,并且在室温下稳定6 h以上.99Tcm(L3,L1a)和99Tcm(L3,L1b)的小鼠生物分布研究表明两种混配复合物都可通过正常的血脑屏障,并在脑中有一定滞留. 相似文献
5.
Sodium 3-ferrocenyl-5-phenyl-pyrazoline-1-dithiocarbamate (FPPD) reacts with anhydrousrare earth chlorides in absolute ethanol to give 14 new complexes.The results of elemental analysis show thatthe compositions of the complexes are RE(FPPD)_3·nH_2O(RE=La,Pr~Lu and Y;n=3).The ligand andits complexes have been characterized by infrared spectroscopy,UV-visible absorptionspectroscopy,~1H-NMR spectra,thermal analysis and molar conductivity measurement. 相似文献
6.
Binding Properties of RNA Quadruplex of SARS-CoV-2 to Berberine Compared to Telomeric DNA Quadruplex
Rosario Oliva Sanjib Mukherjee Magiliny Manisegaran Marco Campanile Pompea Del Vecchio Luigi Petraccone Roland Winter 《International journal of molecular sciences》2022,23(10)
Previous studies suggest that berberine, an isoquinoline alkaloid, has antiviral potential and is a possible therapeutic candidate against SARS-CoV-2. The molecular underpinnings of its action are still unknown. Potential targets include quadruplexes (G4Q) in the viral genome as they play a key role in modulating the biological activity of viruses. While several DNA-G4Q structures and their binding properties have been elucidated, RNA-G4Qs such as RG-1 of the N-gene of SARS-CoV-2 are less explored. Using biophysical techniques, the berberine binding thermodynamics and the associated conformational and hydration changes of RG-1 could be characterized and compared with human telomeric DNA-G4Q 22AG. Berberine can interact with both quadruplexes. Substantial changes were observed in the interaction of berberine with 22AG and RG-1, which adopt different topologies that can also change upon ligand binding. The strength of interaction and the thermodynamic signatures were found to dependent not only on the initial conformation of the quadruplex, but also on the type of salt present in solution. Since berberine has shown promise as a G-quadruplex stabilizer that can modulate viral gene expression, this study may also contribute to the development of optimized ligands that can discriminate between binding to DNA and RNA G-quadruplexes. 相似文献
7.
Andrea Bagn Jos A. Morales-García Christian Grin-Ferr Caridad Díaz Jos Prez del Palacio Maria C. Ramos Francisca Vicente Beln Prez Jos Brea María Isabel Loza Merc Palls Carmen Escolano 《International journal of molecular sciences》2022,23(10)
The impact of neurodegenerative diseases (ND) is becoming unbearable for humankind due to their vast prevalence and the lack of efficacious treatments. In this scenario, we focused on imidazoline I2 receptors (I2-IR) that are widely distributed in the brain and are altered in patients with brain disorders. We took the challenge of modulating I2-IR by developing structurally new molecules, in particular, a family of bicyclic α-iminophosphonates, endowed with high affinity and selectivity to these receptors. Treatment of two murine models, one for age-related cognitive decline and the other for Alzheimer’s disease (AD), with representative compound B06 ameliorated their cognitive impairment and improved their behavioural condition. Furthermore, B06 revealed beneficial in vitro ADME-Tox properties. The pharmacokinetics (PK) and metabolic profile are reported to de-risk B06 for progressing in the preclinical development. To further characterize the pharmacological properties of B06, we assessed its neuroprotective properties and beneficial effect in an in vitro model of Parkinson’s disease (PD). B06 rescued the human dopaminergic cell line SH-SY5Y from death after treatment with 6-hydroxydopamine (6-OHDA) and showed a crucial anti-inflammatory effect in a cellular model of neuroinflammation. This research reveals B06 as a putative candidate for advancing in the difficult path of drug discovery and supports the modulation of I2-IR as a fresh approach for the therapy of ND. 相似文献
8.
Sung-Min Hwang Youn-Yi Jo Cinder Faith Cohen Yong-Ho Kim Temugin Berta Chul-Kyu Park 《International journal of molecular sciences》2022,23(10)
The transient receptor potential vanilloid 1 (TRPV1) ion channel plays an important role in the peripheral nociceptive pathway. TRPV1 is a polymodal receptor that can be activated by multiple types of ligands and painful stimuli, such as noxious heat and protons, and contributes to various acute and chronic pain conditions. Therefore, TRPV1 is emerging as a novel therapeutic target for the treatment of various pain conditions. Notably, various peptides isolated from venomous animals potently and selectively control the activation and inhibition of TRPV1 by binding to its outer pore region. This review will focus on the mechanisms by which venom-derived peptides interact with this portion of TRPV1 to control receptor functions and how these mechanisms can drive the development of new types of analgesics. 相似文献
9.
Binuclear aluminum complex as an efficient orange emitter in single-layer electroluminescent devices
A binuclear aluminum complex with a chelating anilido-imine conjugated Schiff base ligand, 1,4-{o-C6H4[N(2,6-iPr2C6H3)][CH N]Al(CH3)2}2C6H4 (3), was synthesized from the alkane elimination reaction of trimethylaluminum with the free ligand, 1,4-{o-C6H4[NH(2,6-iPr2C6H3)][CH N]}2C6H4 (2), at room temperature. The photophysical properties of complex 3 were briefly examined and it was found that complex 3 displays bright orange luminescence in solution and in solid state. Electroluminescent devices were fabricated by doping complex 3 in polymer blend host of poly(vinylcarbazole) and 2-tert-butylphenyl-5-biphenyl-1,3,4-oxadiazol using simple solution spin-coating technique. Efficient orange light emission was obtained from the fabricated single-layer organic light-emitting devices with a maximum current efficiency of 3.2 cd/A. 相似文献
10.
The management of chronic liver diseases (CLDs) remains a challenge, and identifying effective treatments is a major unmet medical need. In the current review we focus on the pituitary tumor transforming gene (PTTG1)/delta like non-canonical notch ligand 1 (DLK1) axis as a potential therapeutic target to attenuate the progression of these pathological conditions. PTTG1 is a proto-oncogene involved in proliferation and metabolism. PTTG1 expression has been related to inflammation, angiogenesis, and fibrogenesis in cancer and experimental fibrosis. On the other hand, DLK1 has been identified as one of the most abundantly expressed PTTG1 targets in adipose tissue and has shown to contribute to hepatic fibrosis by promoting the activation of hepatic stellate cells. Here, we extensively analyze the increasing amount of information pointing to the PTTG1/DLK1 signaling pathway as an important player in the regulation of these disturbances. These data prompted us to hypothesize that activation of the PTTG1/DLK1 axis is a key factor upregulating the tissue remodeling mechanisms characteristic of CLDs. Therefore, disruption of this signaling pathway could be useful in the therapeutic management of CLDs. 相似文献