Optimizing the structural features of the dioxygenated benzo lead compound
Ontology highlight
ABSTRACT:
ORGANISM(S): Escherichia Coli
SUBMITTER: 
Rui Wang
PROVIDER: PXD057976 | iProX | Mon Nov 18 00:00:00 GMT 2024
REPOSITORIES: iProX
Similar Datasets
Project description:The E2F family of transcription factors is typically described as binding the family consensus sequence TTTSSCGC, were S is G or C. Analysis of ChIP-seq experiments, however, reveals that this consensus sequence is found in only 10% of ChIP-seq peaks, suggesting that the mechanism for E2F sequence recognition cannot be explained using previous assumptions. In order to better understand E2F sequence specificity, we performed high-throughput Universal Protein Binding Microarray experiments to obtain the relative binding affinity for every possible 8-mer, as well a large number of bound and unbound probes intheir native genomic sequence context. Our results show that while the consensus sequence is bound with relatively high affinity, numerous other 8-mers, many distinctly different from the consensus motif, are bound with similar or greater affinity. These data suggest that the mechanism for E2F sequence specificity is likely complex, and cannot readily be explained through a simple consensus sequence. Because of this, complex regression models were created using the bound and unbound probe binding affinities, and were able to predict binding in vivo, where the consensus sequence and varoius E2F PWMs were not.
2014-11-04 | GSE61854 | GEO
Project description:A novel approach toward the protection of affinity purification matrices, such as the protein streptavidin or immunoglobulins, from tryptic digestion. This allows for on-bead enzymatic digestion, while minimizing contamination from the affinity purification matrix.
2018-11-27 | MSV000083168 | MassIVE
Project description:Transcription factors (TFs) regulate gene expression by interacting with DNA in a sequence-specific manner. High-throughput in vitro technologies, such as PBMs and HT-SELEX, have revealed the DNA binding specificities of hundreds of TFs. However, they have limited ability to reliably identify lower affinity binding sites, which are increasingly recognized as important for precise spatial and temporal control of gene expression. To address this limitation, we developed a novel technology to measure protein affinity to DNA by in vitro transcription and RNA sequencing (PADIT-seq). Using PADIT-seq, we comprehensively assayed the binding preferences of four human and two yeast TFs to all possible 10-bp DNA sequences, detecting hundreds of novel lower affinity binding sites. The expanded repertoire of lower affinity binding sites unexpectedly revealed that nucleotides flanking high affinity DNA binding sites create overlapping lower affinity sites that together modulate TF genomic occupancy in vivo. We propose a model where TF binding is not determined by individual binding sites, but rather by the sum of multiple, overlapping binding sites. Formation of such extended recognition sequences stems from an inherent property of TF binding sites to interweave each other. Consequently, competition between paralogous TFs for shared high-affinity binding sites is controlled by flanking nucleotides that create differential numbers of overlapping lower affinity binding sites. Noncoding variants alter multiple, overlapping binding sites to influence gene expression and human traits, including diseases.
2024-03-06 | GSE250601 | GEO
Project description:Among neglected tropical diseases, leishmaniasis is one of the leading causes, not only of deaths but also of disability-adjusted life years. This disease, caused by protozoan parasites of the genus Leishmania, triggers different clinical manifestations, with cutaneous, mucocutaneous, and visceral forms. As existing treatments for this parasitosis are not sufficiently effective or safe for the patient, in this work, different sesquiterpenes isolated from the red alga Laurencia johnstonii have been studied for this purpose. The different compounds were tested in vitro against the promastigote and amastigote forms of Leishmania amazonensis. Different assays were also performed, including the measurement of mitochondrial potential, determination of ROS accumulation, and chromatin condensation, among others, focused on the detection of the cell death process known in this type of organism as apoptosis-like. Five compounds were identified that displayed leishmanicidal activity: laurequinone, laurinterol, debromolaurinterol, isolaurinterol, and aplysin, showing IC50 values against promastigotes of 1.87, 34.45, 12.48, 10.09, and 54.13 µM, respectively. Laurequinone was the most potent compound tested and was shown to be more effective than the reference drug miltefosine against promastigotes. Different death mechanism studies carried out showed that laurequinone appears to induce programmed cell death or apoptosis in the parasite studied. The obtained results underline the potential of this sesquiterpene as a novel anti-kinetoplastid therapeutic agent.
| S-EPMC10304164 | biostudies-literature
Project description:Low affinity CTCF binding drives transcriptional regulation whereas high affinity binding encompasses architectural functions.
| PRJNA856492 | ENA
Project description:A comprehensive optical description of compound refractive lenses (CRLs) in condensing and full-field X-ray microscopy applications is presented. The formalism extends ray-transfer matrix analysis by accounting for X-ray attenuation by the lens material. Closed analytical expressions for critical imaging parameters such as numerical aperture, spatial acceptance (vignetting), chromatic aberration and focal length are provided for both thin- and thick-lens imaging geometries. These expressions show that the numerical aperture will be maximized and chromatic aberration will be minimized at the thick-lens limit. This limit may be satisfied by a range of CRL geometries, suggesting alternative approaches to improving the resolution and efficiency of CRLs and X-ray microscopes.
| S-EPMC5330290 | biostudies-literature
Project description:Tislelizumab is an anti-PD-1 monoclonal antibody with high binding affinity for PD-1 and with minimized Fcγ receptor binding on macrophages. Regorafenib has been approved in mCRC by CFDA. Hepatic arterial infusion chemotherapy has a high local control rate for liver metastases. NCCN guidelines and several expert consensus recommend that regional hepatic arterial infusion chemotherapy can be considered as a "rescue treatment" for patients with colorectal cancer liver metastases who fail to receive first-line or second-line systemic chemotherapy, which can significantly prolong the overall survival of patients.
| 61421 | ecrin-mdr-crc
Project description:Strigolactones (SLs) are carotenoid-derived plant hormones involved in the development of various plants. SLs also stimulate seed germination of the root parasitic plants, Striga spp. and Orobanche spp., which reduce crop yield. Therefore, regulating SL biosynthesis may lessen the damage of root parasitic plants. Biosynthetic inhibitors effectively control biological processes by targeted regulation of biologically active compounds. In addition, biosynthetic inhibitors regulate endogenous levels in developmental stage- and tissue-specific manners. To date, although some chemicals have been found as SL biosynthesis inhibitor, these are derived from only three lead chemicals. In this study, to find a novel lead chemical for SL biosynthesis inhibitor, 27 nitrogen-containing heterocyclic derivatives were screened for inhibition of SL biosynthesis. Triflumizole most effectively reduced the levels of rice SL, 4-deoxyorobanchol (4DO), in root exudates. In addition, triflumizole inhibited endogenous 4DO biosynthesis in rice roots by inhibiting the enzymatic activity of Os900, a rice enzyme that converts the SL intermediate carlactone to 4DO. A Striga germination assay revealed that triflumizole-treated rice displayed a reduced level of germination stimulation for Striga. These results identify triflumizole as a novel lead compound for inhibition of SL biosynthesis.
| S-EPMC7728069 | biostudies-literature
Project description:The functionality of proteins is dependent on their spatial and temporal distributions, neither of which is directly measured by static protein abundance. Here we report a mass spectrometry-based proteomics workflow and data analysis pipeline, named Simultaneous Proteome Localization and Turnover (SPLAT), to concurrently examine the turnover dynamics and subcellular distributions of whole cell proteomes under perturbation. SPLAT builds on prior work in protein turnover measurements and subcellular localization profiling, by combining dynamic stable isotope labeling, differential ultracentrifugation, and kinetic modeling to concurrently measure changes in protein turnover and subcellular localization under perturbation in one experiment.
2022-12-31 | PXD038054 | JPOST Repository
Project description:The CXCR4/CXCL12 axis plays prominent roles in tumor metastasis and inflammation. CXCR4 has been shown to be involved in a variety of inflammation-related diseases. Therefore, CXCR4 is a promising potential target to develop novel anti-inflammatory agents. Taking our previously discovered CXCR4 modulator RB-108 as the lead compound, a series of derivatives were synthesized structurally modifying and optimizing the amide and sulfamide side chains. The derivatives successfully maintained potent CXCR4 binding affinity. Furthermore, compounds IIb, IIc, IIIg, IIIj, and IIIm were all efficacious in inhibiting the invasion of CXCR4-positive cells, displaying a much more potent effect than the lead compound RB-108. Notably, compound IIIm significantly decreased carrageenan-induced swollen volume and paw thickness in a mouse paw edema model. More importantly, IIIm exhibited satisfying PK profiles with a half-life of 4.77 h in an SD rat model. In summary, we have developed compound IIIm as a new candidate for further investigation based on the lead compound RB-108.
| S-EPMC6488424 | biostudies-literature