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161.
Synthetic lethality describes situations in which defects in two different genes or pathways together result in cell death. This concept has been applied to drug development for cancer treatment, as represented by Poly (ADP-ribose) polymerase (PARPs) inhibitors. In the current study, we performed a computational screening to discover new PARP inhibitors. Among the 11,247 compounds analyzed, one natural product, ZINC67913374, stood out by its superior performance in the simulation analyses. Compared with the FDA approved PARP1 inhibitor, olaparib, our results demonstrated that the ZINC67913374 compound achieved a better grid score (−86.8) and amber score (−51.42). Molecular dynamics simulations suggested that the PARP1-ZINC67913374 complex was more stable than olaparib. The binding free energy for ZINC67913374 was −177.28 kJ/mol while that of olaparib was −159.16 kJ/mol. These results indicated ZINC67913374 bound to PARP1 with a higher affinity, which suggest ZINC67913374 has promising potential for cancer drug development. 相似文献
162.
A Systematic Structure–Activity Study of a New Type of Small Peptidic Transfection Vector Reveals the Importance of a Special Oxo-Anion-Binding Motif for Gene Delivery 下载免费PDF全文
Dr. Sandra Junghänel Sarah Karczewski Sandra Bäcker Prof. Dr. Shirley K. Knauer Prof. Dr. Carsten Schmuck 《Chembiochem : a European journal of chemical biology》2017,18(22):2268-2279
We discovered a new class of artificial peptidic transfection vectors based on an artificial anion-binding motif, the guanidiniocarbonylpyrrole (GCP) cation. This new type of vector is surprisingly smaller than traditional systems, and our previous work suggested that the GCP group was important for promoting critical endosomal escape. We now present here a systematic comparison of similar DNA ligands featuring our GCP oxo-anion-binding motif with DNA ligands only consisting of naturally occurring amino acids. Structure–activity studies showed that the artificial binding motif clearly outperformed natural amino acids such as histidine, lysine, and arginine. It improved the ability to shuttle foreign genetic material into cells, yet successfully mediated endosomal escape. Also, plasmids that were complexed by our artificial ligands were stabilized against cytosolic degradation to some extent. This resulted in the successful expression of plasmid information (comparable to gold standards such as polyethyleneimine). Hence, our study clearly demonstrates the importance of the tailor-made GCP anion-binding site for efficient gene transfection. 相似文献
163.
DNA within the living cells experiences a diverse range of temperature, ranging from freezing condition to hot spring water. How the structure, the mechanical properties of DNA, and the solvation dynamics around DNA changes with the temperature is important to understand the functionality of DNA under those acute temperature conditions. In that notion, we have carried out molecular dynamics simulations of a DNA oligomer, containing TATA-box sequence for three different temperatures (250 K, 300 K and 350 K). We observed that the structure of the DNA, in terms of backbone torsion angles, sugar pucker, base pair parameters, and base pair step parameters, did not show any unusual properties within the studied range of temperatures, but significant structural alteration was noticed between BI and BII forms at higher temperature. As expected, the flexibility of the DNA, in terms of the torsional rigidity and the bending rigidity is highly temperature dependent, confirming that flexibility increases with increase in temperature. Additionally, the groove widths of the studied DNA showed temperature sensitivity, specifically, the major groove width decreases and the minor groove width increases, respectively, with the increase in temperature. We observed that at higher temperature, water around both the major and the minor groove of the DNA is less structured. However, the water dynamics around the minor groove of the DNA is more restricted as compared to the water around the major groove throughout the studied range of temperatures, without any anomalous behavior. 相似文献
164.
DNA nanostructures can undergo large structural fluctuations and deviate from their intended configurations. In this work, two model DNA nanostructures (i.e., Nan and Kai) were designed based on the shape of the two Chinese characters of the name of Nankai University, and additional single-stranded DNA fragments were added to interact with graphene. During four 50-ns molecular dynamic simulations in aqueous solution, the DNA nanostructures adsorbed onto graphene demonstrated more stable conformations with lower root mean square deviations and smaller coordinate changes in the z-axis direction than the DNA nanostructures that were not adsorbed onto graphene. The interaction analyses and energetic calculations show that π-π interactions between single-stranded DNA and graphene are necessary for adsorption of the DNA nanostructures. Overall, this work examined the interactions between DNA and graphene at a large spatial scale with the hope that it provides a new strategy to stabilize DNA nanostructures. 相似文献
165.
Recently, considerable interest have occurred in the development of an organic-inorganic-based bio-hybrid photodiodes (Bio-HPDs) with metal-free, eco-friendly, and cost-competitive features for light-sensitive devices. This paper reports a bio-inspired optical absorber material for the fabrication of Bio-HPDs using n-type hydrogenated amorphous silicon (a-Si:H) and a natural deoxyribonucleic acid (DNA)-cetyltrimethylammonium chloride (CTMA) biomaterial. a-Si:H is inexpensive and abundant, and DNA-CTMA is metal-free and eco-friendly. A DNA-CTMA coating on n-type a-Si:H leads to a chemically stable material with increased absorption and effective ties of dangling bonds and interface state density. Analysis results showed that the rectification ratio (RR) of the Bio-HPD is found to be 4 times higher than reference PD. This indicates that the effective RR is improved by the DNA-CTMA layer since it creates molecular charge interactions between DNA-CTMA layer and a-Si:H substrate. Moreover, Bio-HPD shows a light photosensitivity (Iphoto/Idark) of 474 with more reliable and has longer life time. In addition, the formation and feasible charge transport mechanisms are discussed. This biomaterial can be used for the development of commercially viable and environmentally safe large-scale Bio-HPDs applications. 相似文献
166.
Laura Baranello Fedor Kouzine Damian Wojtowicz Kairong Cui Teresa M. Przytycka Keji Zhao David Levens 《International journal of molecular sciences》2014,15(7):13111-13122
Genomic DNA is under constant assault by endogenous and exogenous DNA damaging agents. DNA breakage can represent a major threat to genome integrity but can also be necessary for genome function. Here we present approaches to map DNA double-strand breaks (DSBs) and single-strand breaks (SSBs) at the genome-wide scale by two methods called DSB- and SSB-Seq, respectively. We tested these methods in human colon cancer cells and validated the results using the Topoisomerase II (Top2)-poisoning agent etoposide (ETO). Our results show that the combination of ETO treatment with break-mapping techniques is a powerful method to elaborate the pattern of Top2 enzymatic activity across the genome. 相似文献
167.
The charge transport properties of DNA are studied by the first-principle simulation to discuss the possibility of applying DNA to molecular wire. Both the hopping model and band-like model are introduced. By using hopping model, the theoretical hole mobilities calculated by Marcus theory between the same bases in DNA are 5.6 × 10−3, 4.1 × 10−2, 2.0 × 10−2 and 1.2 × 10−4 cm2V−1s−1 for T-T, A-A, C-C and G-G; and the calculated electron mobilities are 5.3 × 10−8, 1.5 × 10−4, 8.1 × 10−7 and 7.5 × 10−10 cm2V−1s−1 for T-T, A-A, C-C and G-G, respectively. And the charge transport for both holes and electrons between different bases exhibits directivity. By using band-like model, we calculated the band width of DNA with double helix structure and bilinear structure to investigate which structure will facilitate to the charge transport. We found that the band width of DNA increased when DNA transforming from the double helix structure to the bilinear structure, which means DNA with the bilinear structure possesses better charge transport properties. This research sheds a light on the molecular design for the molecule serving as the molecular wire. 相似文献
168.
《Food Control》2014
To guarantee consumers about the security of what they eat is the main goal of all the institutions working to assure food safety. In seafood field it appears of prime importance to be able to identify fish species throughout the production cycle also when the product has been already processed (breaded fish, fillets etc). In this context the latest system proposed for species identification is the so called “DNA-Barcoding”, made by carrying out the DNA sequencing of a standard barcode region. In the present study we carried out bi-directional sequence analysis of mitochondrial cytochrome b gene (Cytb) and cytochrome oxidase subunit I gene (COI). The main goal of the research was to unambiguously classify the most common fishes traded in Italy, being able to ascertain possible labeling frauds made substituting value species with less precious ones. With both genes we could correctly identify almost all the samples in study: respectively 58/58 with COI and 56/58 with Cytb. This study confirms mitochondrial genes Cytb and COI as good candidates for fish species identification by DNA sequencing. This method appears particularly suitable especially when morphological characterization is difficult, (for very close species), or impossible (for transformed foodstuffs) to carry out. What's more we could efficiently identify many fishes belonging to the Mediterranean fauna, which, to our knowledge, underwent for the first time this kind of analysis. Further development will concern the extension of the analysis to a largest number of local species. 相似文献
169.
Prof. Mitsunobu Nakamura Dr. Tadao Takada Prof. Kazushige Yamana 《Chembiochem : a European journal of chemical biology》2019,20(23):2949-2954
B- to Z-DNA transitions play a crucial role in biological systems and have attracted the interest of researchers for their applications in DNA nanotechnology. DNA and DNA analogues have also been used as templates to construct helical chromophore associations with π interactions. In this work, the B- to Z-DNA transition-induced switching of pyrene in an association manner was evaluated using DNA duplexes with non-nucleosidic pyrene residues in the middle of d(CG) repeat sequences. One of the pyrene-labeled DNAs was shown to exhibit inverted exciton coupled circular dichroism signals upon pyrene association through a B- to Z-DNA transition. This observation indicates that pyrene association switches the DNA conformation from right- to left-handed. Interestingly, the fluorescence of the pyrene-labeled DNA duplex also dynamically changed upon switching of the pyrene in an association-based manner. Taken together, these studies demonstrate that pyrene-labeled DNA shows promise as a chiroptical molecular switch. 相似文献