57 results about "Helicase" patented technology

Disclosed herein are certain thiadiazolyl derivatives Formula (I):that inhibit DNA Polymerase Theta (Polθ) activity, in particular inhibit Polθ activity by inhibiting ATP dependent helicase domain activity of Polθ. Also, disclosed are pharmaceutical compositions comprising such compounds and methods of treating and / or preventing diseases treatable by inhibition of Polθ such as cancer, including homologous recombination (HR) deficient cancers.

The present invention relates to compounds of the Formula I, and pharmaceutically salts thereof: I wherein RS, R1, R2, R3, R4 and X are each as defined herein. The compounds of the present invention inhibit WRN. The novel therapeutic compounds are therefore useful for the treatment and / or prevention of diseases and conditions in which WRN activity is implicated, such as, for example but not limited to, the treatment and / or prevention of cancer. The present invention also relates to pharmaceutical compositions comprising the novel therapeutic compounds defined herein, to processes for synthesising these compounds and to their use for the treatment of diseases and / or conditions in which WRN activity is implicated.

The present disclosure provides 3,7-disubstituted 2-oxo-2H-chromenyl compounds of Formula I or Formula II as inhibitors of helicases, such as SF3 and / or SF6 helicases, and more particularly, for example, CMG helicase and HPV El helicase, useful in treating medical disorders such as cancers or papilloma virus infections, as well as methods of making and using said compounds.

This disclosure pertains to the field of gene sequencing technology and discloses the KphPif1 helicase and its applications. This disclosure relates to a modified helicase, a polynucleotide encoding the helicase, a recombinant expression vector, and a construct capable of expressing the modified helicase and used to construct recombinant cells expressing the helicase. The modified helicase disclosed herein allows target polynucleotides to pass through nanopores in a controllable and stepwise manner, stabilizing polynucleotide movement and preventing detachment from the polynucleotide. Furthermore, it features a wide current range, high decoding accuracy, fast perforation speed, and high sequencing efficiency.

Provided are a helicase mutant, a preparation method therefor, and use thereof in high-throughput sequencing. The helicase mutant has at least one cysteine on a surface of a three-dimensional structure of an amino acid sequence as set forth in SEQ ID NO: 1, the at least one cysteine being substituted with alanine. The cysteine is C133, C164, C292, C323, and / or C347. Preferably, the amino acid sequence of the helicase mutant is as set forth in SEQ ID NO: 6. The helicase mutant exhibits excellent DNA unwinding activity, good protein uniformity, reduced cross-linking interactions between protein molecules, enhanced adaptability with perforin, improved sequencing stability, as well as integrity and continuity of electrical signals. Consequently, it achieves a better sequencing performance. It can be utilized for the control and characterization of nucleic acids and applied in single-molecule nanopore sequencing.

The present disclosure provides technologies for genetic modification that use a helicase beta-wing element (HbW element). Provided technologies enable genetic modification without a need for introduction of one or more breaks into any genetic material being modified.

The invention discloses pharmaceutical application of RNA helicase DHX8, including application of the RNA helicase DHX8 in aortic dissection diagnosis, treatment and drug development. It is found for the first time that DHX8 is significantly down-regulated in aortic dissection patients, animal models and vascular endothelial cells, and overexpression of DHX8 can effectively up-regulate endothelial cell tight connection related genes and repair the endothelial barrier function. The Si DHX8 is used for transfecting human umbilical vein endothelial cells (HUVECs), and the DHX8 is knocked down, so that the tight connection gene OCLN is obviously reduced; when the OE DHX8 plasmid is used for transfecting the HUVECs and overexpressing the DHX8, the tight connection genes OCLN, JAM-A, ZO-1 and VE-cadherin are found to be obviously up-regulated. The DHX8 is used as a new target for aortic dissection diagnosis and treatment, and a detection reagent, a gene therapy vector and an agonist drug of the DHX8 have important clinical transformation values.

The disclosure provides compounds of Formula I or pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising such compounds, and use of such compounds for treating cancers treatable by inhibition of WRN helicase.

This invention discloses a method for rice to withstand heat stress. RMI1 Genes and their applications. Among them... RMI1 The nucleotide sequence of the gene is shown in SEQ ID No. 1, and the amino acid sequence of the protein it encodes is shown in SEQ ID No. 2; this invention verifies RMI1 The function of the gene, RMI1 protein is located in the cell nucleus, rmi1-1 In mutants RMI1 The deletion of 33 base pairs in the gene results in the loss of 11 amino acids in the RMI1-1 protein, making... rmi1-1 High temperatures during the seedling stage cause a large number of abnormal chromosomes to adhere and fragment during the late mitotic phase of root tip cells, resulting in stunted plant growth and development. rmi1-1 High temperatures during the reproductive growth period of plants lead to a large number of chromosome fragments and adhesions in the late stage of meiosis I, resulting in sterility; high temperatures also affect the interaction between RMI1-1 protein and topoisomerase TOP3α and helicase RECQ4. rmi1-cr3 Frameshift mutations lead to abnormal embryo and endosperm development; overexpression RMI1 This invention can enhance the heat resistance of rice. RMI1 The analysis of gene function provides genetic resources for the breeding of heat-resistant rice varieties.

Provided is a method for predicting sensitivity of a cancer cell to a helicase inhibitor, the method comprising the step of:predicting a cancer cell having at least one mutation detected selected from the first group consisting of TTK mutation and RAD 50 mutation, as having sensitivity to a helicase inhibitor, orpredicting a cancer cell having at least one mutation detected selected from the second group consisting of RAD 50 mutation, MRE 11 mutation, NBN mutation, DNA 2 mutation and RBBP 8 mutation, as having sensitivity to a helicase inhibitor.

This invention application discloses a gene regulating maize kernel development. ZmRH51 This application focuses on the encoded proteins, functional markers, and applications of maize kernel mutants. m223 Using this as the basic material, its heterozygotes were crossed with Zheng 58 (Z58) to construct the F2 segregating population. Phenotypic identification and cytological observation were performed on the progeny segregating population. Controlling populations were obtained through genetic analysis, BSR-seq analysis, and map-based cloning. m223 Genes with mutant phenotypes ZmRH51 This gene is located in the nucleolar region and encodes an RNA helicase belonging to the DEAD-Box gene family. Studies have shown that... ZmRH51 It participates in ribosome assembly and can influence the processing of pre-rRNA in maize kernels; and further mining yields... ZmRH51 The superior allelic variant genotype of this gene in terms of grain thickness can be utilized to improve grain thickness and 100-grain weight, thereby increasing yield. Furthermore, the distribution and utilization potential of different haplotypes in inbred lines were studied, providing technical support and excellent germplasm resources for the utilization of this gene.

The invention discloses an RNA helicase inhibitor purification process based on solvent extraction, and relates to the technical field of RNA helicase inhibitors, the RNA helicase inhibitor purification process comprises a shell, an extractor, a washer, a first motor, a first delivery pipe, a first discharge pipe, a first rotating rod, a first stirring impeller and a liquid pump; the extractor is fixedly connected to the interior of the shell; the washer is fixedly connected to the right side of the extractor in the shell; an extraction function and a washing function are integrated in the same device through an integrated structural design, and an extracted solvent phase containing a target object can directly enter a washing link in the device without being transferred, so that the problems of microbial pollution, target object activity loss and residue loss caused by a transfer process in a traditional step-by-step process are effectively avoided; the purification yield and the product purity are obviously improved; the operation process is greatly simplified, the production cycle is shortened, the process complexity and the production cost are reduced, and the stability and the practicability of the RNA helicase inhibitor purification process are integrally improved.

Protein complexes including a cytidine deaminase and a helicase. In some embodiments, the cytidine deaminase is an altered cytidine deaminase. In some embodiments, the protein complex converts 5 methylcytosine to thymine. Kits, compositions, and methods of use for the protein complexes including a cytidine deaminase and a helicase are also described.

Provided in the present invention are a nitrogen-containing compound for inhibiting WRN helicase, a pharmaceutical composition containing same, and a use thereof. Specifically, provided in the present invention are a compound shown in formula (I), a stereoisomer thereof, an optical isomer thereof, a pharmaceutically acceptable salt thereof, a crystal form thereof, an isotopic derivative thereof, a prodrug thereof, a metabolite thereof, and a solvate or a hydrate thereof. Also provided are a composition containing the compound and the use thereof as a WRN helicase inhibitor in the prevention or treatment of related diseases.

The application discloses a novel radionuclide therapeutic drug targeting nucleolus DDX24 helicase and a preparation method and application thereof. 64 The Cu-DOTA-TDP-2 has good tumor targeting uptake specificity, and is expected to provide a precise molecular imaging method for esophageal squamous cell carcinoma and other DDX24 high-expression malignant tumors; the novel radionuclide targeted drug 177 The Lu-DOTA-TDP-2 has high radiochemical yield and specific activity, good chemical stability, high affinity for DDX24 helicase, and a simple and easy-to-operate preparation method, and can be used for the treatment of DDX24 high-expression malignant tumors; the novel radionuclide targeted drug 177 The Lu-DOTA-TDP-2 has excellent biological safety performance and good tumor inhibition effect in esophageal squamous cell carcinoma and other DDX24 high-expression malignant tumors.

The application discloses a spiro derivative as a WRN helicase inhibitor and application thereof. The spiro derivative has better WRN helicase inhibiting activity, can be used for inhibiting the growth of microsatellite instability (MSI) tumor cells by inhibiting WRN to cause high levels of DNA double-strand breaks (DSB) in the MSI cells, can be used for preventing and / or treating related cancers, especially colorectal cancer, gastric cancer, ovarian cancer and endometrial tumor, can fill the gap of specific MSI typing cancer targeting drugs, and has very good application prospect and value in the medical field.

The invention discloses a method for screening a controllable CcdB suicide switch based on deep learning, and belongs to the technical field of biology. According to the invention, a deep learning tool MuToN mutant and DNA helicase binding energy change is used for prediction and sorting, mutants with obvious decline in affinity are screened, the obtained mutants are constructed into an expression plasmid containing an inducible promoter through a site-specific mutagenesis method, the expression plasmid is transformed into an MG1655 bacterium lacking a detoxification gene ccdA, and under the condition of not adding an inducer, the expression plasmid containing the inducible promoter is transformed into the MG1655 bacterium lacking the detoxification gene ccdA, and the expression plasmid containing the inducible promoter is transformed into the MG1655 bacterium lacking the detoxification gene ccdA. Screening a strain-free toxic mutant through a coating method; the obtained mutant plasmid is transformed into MG1655 bacteria without a detoxification gene ccdA, a flat plate containing anhydrotetracycline is coated with the MG1655 bacteria, and a mutant with a high fatality rate is screened. A mutant which is moderate in toxicity, can be expressed under the background of lacking CcdA and can reactivate toxicity under an induction condition is constructed, so that a controllable suicide mechanism is realized, and the mutant can be used for on-demand self-killing of strains, construction of gRNA plasmids in a CRISPR / Cas system and sterile treatment of fermentation waste liquid.

The present invention relates to: a pharmaceutical composition for preventing or treating cancer, wherein the composition specifically inhibits ERCC3 (ERCC Excision Repair 3, TFIH Core Complex Helicase Subunit, also referred to as Xeroderma pigmentosum group B (XPB)) to inhibit the proliferation of cancer cells while inducing normal differentiation, thereby reverting the cancer cells into normal-like cells (or normal functional cells); and a method for screening a drug for reverting cancer cells into normal-like cells (or normal functional cells) by inhibiting the proliferation of the cancer cells while inducing normal differentiation.

The invention belongs to the technical field of biological detection, and particularly relates to an ultrashort helicase dependent isothermal amplification detection reagent based on CRISPR / Cas12a. According to the invention, a large amount of ultrashort amplicons are generated through the usHDA reaction and are combined with the CRISPR / Cas12a detection technology, the reaction is rapid, the whole experiment time does not exceed one hour, the experiment time is greatly shortened, the defect of insufficient specificity of the traditional HDA technology is overcome, the uncovering operation is avoided, and the pollution risk is reduced.

This invention relates to a novel mRNA composition and its production method useful for developing and manufacturing RNA-based anti-viral and / or anti-cancer vaccines and medicines. This invention includes two types of mRNA constructs, namely “5′-hairpin messenger RNA (5hmRNA)” and “messenger-hairpin-messenger RNA (mhmRNA)”, respectively. Both of 5hmRNA and mhmRNA contain at least a hairpin-like stem-loop RNA structure. The 5hmRNA contains at least a stem-loop RNA structure in the 5′-UTR of a protein / peptide-coding mRNA, while the mhmRNA contains a middle stem-loop structure flanked with two protein / peptide-coding mRNA sequences on both sides. In mhmRNA, the first 5′-mRNA preferably encodes an RNA replicase, for amplifying the second 3′-mRNA in transfected cells. After transfection into target cells, 5hmRNA and mhmRNA can be further translated into at least a desired protein / peptide. To produce highly structured 5hmRNA and mhmRNA, a novel PCR-IVT methodology has been developed and used with a specially designed RNA polymerase-helicase mixture reaction.

A method of increasing an amount of Chromodomain Helicase DNA Binding Protein 2 (CHD2) in a neuronal cell is provided. The method comprising introducing into the cell a nucleic acid agent directed at the last exon of human Chaserr, thereby increasing the amount of CHD2 in the neuronal cell.

Disclosed are heteroaryl compounds having the structure shown in the following formula (I), and stereoisomers, reciprocal isomers, N-oxides, hydrates, solvates, isotopically labeled compounds or pharmaceutically acceptable salts, or mixtures thereof, which could be used as inhibitors of nucleic acid deconjugating enzyme DHX9 for the treatment or prevention of DHX9-related diseases, such as cancer.

The present disclosure relates generally to the enzymatic conversion of methylated nucleic acids in order to differentiate methylated cytosine from unmethylated cytosine in DNA, and more particularly to improved methods and compositions for enzymatic methylation sequencing. In one aspect, various compositions and methods for improving the recovery of methylation signals are provided. The methods include one or more of a nick repair step, methylation signal restoration, use of a modified methylcytosine nucleic acid adapter, and use of a helicase, an ssDNA binding protein, an engineered DNA ligase, or a combination thereof.

The invention belongs to the field of biological agriculture, and relates to application of helicase PbDDX15-like in prevention and control of clubroot. According to the invention, a core gene of plasmodiophora brassicae ZJ-1 is compared with a brewer's yeast protein sequence, a gene DEAD-box RNA helicase (DEAD-box RNA helicase 15-like, PbDDX15-like) which may have a lethal effect on plasmodiophora brassicae is screened out, an RNAi vector of the gene is constructed by using an HIGS technology, and the RNAi vector is transformed into wild type arabidopsis thaliana. The PbDDX15-like-RNAi transgenic arabidopsis thaliana is subjected to a plasmodiophora brassicae disease resistance experiment, and the result shows that the PbDDX15-like-RNAi transgenic arabidopsis thaliana has remarkable resistance to plasmodiophora brassicae, so that the protein can provide a new gene resource for green prevention and resistance of the rape clubroot.

The invention belongs to the field of biological medicine, and discloses a broad-spectrum anti-enterovirus peptidomimetic 2CA-1 targeting enterovirus 2C protein and application of the broad-spectrum anti-enterovirus peptidomimetic 2CA-1. The 2CA-1 can be accurately butted to 2C protein binding pockets of EV71 and CVB3, the helicase activity of the 2CA-1 is effectively inhibited, and the 2CA-1 shows a strong and broad-spectrum antiviral effect on various pathogens such as coxsackie virus, EV-D68 and rhinovirus on the cellular level. More importantly, the 2CA-1 realizes a druggability breakthrough of excellent oral bioavailability in an animal model, and the in-vivo virus load can be remarkably reduced after oral administration. The invention provides an antiviral candidate drug with high-efficiency broad-spectrum activity and ideal oral administration characteristics, and has a wide application prospect.

A method and composition for treating viral infections using a combination of naturally occurring compounds is provided. The method includes administering to a patient at risk of or diagnosed with a viral infection a composition including therapeutically effective amounts of a helicase ATPase inhibitor, a sialidase enzyme inhibitor, an ICAM-1 inhibitor and gallic acid which each also down regulate the immune response. The composition may further include a permeation enhancer.

The present disclosure generally relates to the treatment of subjects having pan-cancer phenotype or at risk of developing pan-cancer phenotype by administering a Regulator of Telomere Elongation Helicase 1 (RTEL1) inhibitor to the subject.

Provided herein are combinations of polymerase theta (Polθ) helicase inhibitors and second therapeutic agents and methods comprising administering to a subject in need thereof such combinations for the treatment of cancer.

The present invention relates to modified Dda helicases that can be used to control the movement of analytes, such as polynucleotides. The modified Dda helicase is used for analyte detection and characterization.

The present disclosure generally relates to the treatment of subjects having pan-cancer phenotype or at risk of developing pan-cancer phenotype by administering a Regulator of Telomere Elongation Helicase 1 (RTEL1) inhibitor to the subject.