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1.
Quan-Qi Yu Juan-Juan Gao Xue-Xian Lang Hong-Yao Li Prof. Ming-Qi Wang 《Chembiochem : a European journal of chemical biology》2021,22(6):1042-1048
The development of small molecules that can selectively target G-quadruplex (G4) DNAs has drawn considerable attention due to their unique physiological and pathological functions. However, only a few molecules have been found to selectively bind a particular G4 DNA structure. We have developed a fluorescence ligand Q1 , a molecular scaffold with a carbazole–pyridine core bridged by a phenylboronic acid side chain, that acts as a selective ascaris telomere antiparallel G4 DNA ASC20 ligand with about 18 nm blue-shifted and enhanced fluorescence intensity. Photophysical properties revealed that Q1 was sensitive to the microenvironment and gave the best selectivity to ASC20 with an equilibrium binding constant Ka=6.04×105 M−1. Time-resolved fluorescence studies also demonstrated that Q1 showed a longer fluorescence lifetime in the presence of ASC20. The binding characteristics of Q1 with ASC20 were shown in detail in a fluorescent intercalator displacement (FID) assay, a 2-Ap titration experiment and by molecular docking. Ligand Q1 could adopt an appropriate pose at terminal G-quartets of ASC20 through multiple interactions including π–π stacking between aromatic rings; this led to strong fluorescence enhancement. In addition, a co-staining image showed that Q1 is mainly distributed in the cytoplasm. Accordingly, this work provides insights for the development of ligands that selectively targeting a specific G4 DNA structure. 相似文献
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Maria Rita Gulotta Serena Vittorio Rosaria Gitto Ugo Perricone Laura De Luca 《International journal of molecular sciences》2021,22(4)
The modulation of protein-protein interactions (PPIs) by small molecules represents a valuable strategy for pharmacological intervention in several human diseases. In this context, computer-aided drug discovery techniques offer useful resources to predict the network of interactions governing the recognition process between protein partners, thus furnishing relevant information for the design of novel PPI modulators. In this work, we focused our attention on the MUC1-CIN85 complex as a crucial PPI controlling cancer progression and metastasis. MUC1 is a transmembrane glycoprotein whose extracellular domain contains a variable number of tandem repeats (VNTRs) regions that are highly glycosylated in normal cells and under-glycosylated in cancer. The hypo-glycosylation fosters the exposure of the backbone to new interactions with other proteins, such as CIN85, that alter the intracellular signalling in tumour cells. Herein, different computational approaches were combined to investigate the molecular recognition pattern of MUC1-CIN85 PPI thus unveiling new structural information useful for the design of MUC1-CIN85 PPI inhibitors as potential anti-metastatic agents. 相似文献
4.
Herein, this paper reports a facile method to prepare electrospun carbon nanofiber mats (ECNFMs) with high specific surface area and interconnected structure using polyacrylonitrile (PAN) as a precursor and novolac resin (NOC) as a polymer sacrificial pore-making agent. Without additional treatment, the prepared ECNFMs have a highly porous structure because NOC decomposes in a wider temperature range than most polymer activators. The NOC content in the PAN nanofibers shows important effects on porosity. The BET specific surface area of ECNFMs reaches a maximum of 1468 m2 g−1 when the precursor nanofibers contained 30 wt% NOC (ECNFM-3) after carbonization at 1000 °C. The supercapacitor device from ECNFM-3 electrode and all-solid-state electrolyte shows excellent cycling durability and high specific capacitance: ≈99.72% capacitance retention after 10 000 charge/discharge cycles and ≈320 mF cm−2 at 0.25 mA cm−2. Furthermore, it shows a large energy density of ≈11.1 Wh cm−2 under the power density of 500 mW m−2. Activation of carbon nanofibers simply by the addition of NOC into precursor nanofibers can offer a handy way to prepare ECNFMs for high-performance all-solid-state supercapacitors and other potential applications. 相似文献
5.
Anna Sib Tobias M. Milzarek Alexander Herrmann Dr. Lila Oubraham Jonas I. Müller Prof. Dr. Andreas Pichlmair Prof. Dr. Ruth Brack-Werner Prof. Dr. Tobias A. M. Gulder 《Chembiochem : a European journal of chemical biology》2020,21(4):492-495
Sorbicillinoids are fungal polyketides characterized by highly complex and diverse molecular structures, with considerable stereochemical intricacy combined with a high degree of oxygenation. Many sorbicillinoids possess promising biological activities. An interesting member of this natural product family is sorbicatechol A, which is reported to have antiviral activity, particularly against influenza A virus (H1N1). Through a straightforward, one-pot chemoenzymatic approach with recently developed oxidoreductase SorbC, the characteristic bicyclo[2.2.2]octane core of sorbicatechol is structurally diversified by variation of its natural 2-methoxyphenol substituent. This facilitates the preparation of a focused library of structural analogues bearing substituted aromatic systems, alkanes, heterocycles, and ethers. Fast access to this structural diversity provides an opportunity to explore the antiviral potential of the sorbicatechol family. 相似文献
6.
Dr. Tom Baladi Dr. Nedra Hamouda-Tekaya Dr. Leticia Christina Pires Gonçalves Dr. Stéphane Rocchi Dr. Cyril Ronco Dr. Rachid Benhida 《ChemMedChem》2020,15(13):1113-1117
Sulfonylguanidines are interesting bioactive compounds with a broad range of applications in the treatment of different pathologies. 2-Aminobenzazole-based structures are well employed in the development of new anticancer drugs. Two series of novel N-benzazol-2-yl-N′-sulfonyl guanidine derivatives were synthesized with the sulfonylguanidine in either an extra- or intracyclic frame. They were evaluated for their antiproliferative activity against malignant melanoma tumor cells, thus allowing structure-activity relationships to be defined. Additionally, NCI-60 screening was performed for the best analogue to study its efficiency against a panel of other cancer cell lines. The stability profile of this promising compound was then validated. During the synthetic process, an unexpected new deamidination of the sulfonylguanidine towards sulfonamide function was also identified. 相似文献
7.
Prof. Chiara Brullo Dr. Federica Rapetti Prof. Silvana Alfei Dr. Irena Maric Dr. Francesca Rizzelli Dr. Marina Mapelli Dr. Camillo Rosano Dr. Maurizio Viale Prof. Olga Bruno 《ChemMedChem》2020,15(11):961-969
Even though immunotherapy has radically changed the search for anticancer therapies, there are still many different pathways that are open to intervention with traditional small molecules. To expand our investigation in the anticancer field, we report here a new series of compounds in which our previous pyrazole and imidazopyrazole scaffolds are linked to a differently decorated phenyl ring through an acylhydrazone linker. Preliminary tests on the library were performed at the National Cancer Institute (USA) against the full NCI 60 cell panel. The best compounds among the imidazopyrazole series were then tested by immunofluorescence staining for their inhibition of cell proliferation, apoptosis induction, and their effect on the cell cycle and on microtubules. Two compounds, in particular 4-benzyloxy-3-methoxybenzyliden imidazopyrazole-7-carbohydrazide showed good growth inhibition, with IC50 values in the low-micromolar range, and induced apoptosis. Both compounds altered the cell-cycle phases with the appearance of polyploid cells. Immunofluorescence analysis evidenced microtubules alterations; tubulin polymerization assays and docking studies suggested the tubulin system to be the possible, although not exclusive, target of the new acylhydrazone series reported here. 相似文献
8.
Sinenhlanhla N. Mthembu Dr. Anamika Sharma Prof. Fernando Albericio Prof. Beatriz G. de la Torre 《Chembiochem : a European journal of chemical biology》2020,21(14):1947-1954
Cysteine is present in a large number of natural and synthetic (bio)molecules. Although the thiol side chain of Cys can be in a free form, in most cases it forms a disulfide bond either with a second Cys (bridge) or with another thiol, as in the case of protecting groups. Efficient reduction of these disulfide bridges is a requirement for many applications of Cys-containing molecules in the fields of chemistry and biochemistry. Here we review reducing methods for disulfide bonds, taking into consideration the solubility of the substrates when selecting the appropriate reducing reagent. 相似文献
9.
Dr. Tommaso Felicetti Prof. Giuseppe Manfroni Prof. Violetta Cecchetti Dr. Rolando Cannalire 《ChemMedChem》2020,15(24):2391-2419
Infections by flaviviruses, such as Dengue, West Nile, Yellow Fever and Zika viruses, represent a growing risk for global health. There are vaccines only for few flaviviruses while no effective treatments are available. Flaviviruses share epidemiological, structural, and ecologic features and often different viruses can co-infect the same host. Therefore, the identification of broad-spectrum inhibitors is highly desirable either for known flaviviruses or for viruses that likely will emerge in the future. Strategies targeting both virus and host factors have been pursued to identify broad-spectrum antiflaviviral agents. In this review, we describe the most promising and best characterized targets and their relative broad-spectrum inhibitors, identified by drug repurposing/libraries screenings and by focused medicinal chemistry campaigns. Finally, we discuss about future strategies to identify new broad-spectrum antiflavivirus agents. 相似文献
10.
针对传统相变微胶囊后整理法制备蓄热调温纺织品时存在制备工序繁杂、效率低等难点,开发了一种简便快捷的后整理法。选用相变蜡、聚氧乙烯辛基苯酚醚-10(OP-10)乳化剂和水性聚氨酯为主要组分,经高剪切乳化制备蓄热调温功能整理剂,利用浸轧—焙烘方式对棉织物进行整理。优化乳化剂用量、相变蜡与聚氨酯配比及焙烘温度,并测定整理后棉织物及背心的蓄热调温性能。结果表明:当OP-10质量分数为5%,相变蜡与聚氨酯的质量比为1.5∶1,焙烘温度150 ℃时,整理剂在纤维表面原位成膜形成包裹纤维的蓄热调温薄膜,从而赋予棉织物蓄热调温功能;整理后棉织物具备蓄热调温功能,由其所制作的背心具有显著的蓄热调温功能。 相似文献