138 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 invention provides a sequencing linker, a sequencing linker compound and a method for multiple nanopore sequencing of a target nucleic acid sequence. Wherein the sequencing linker comprises a first chain and a second chain, the first chain comprises a sequencing guide sequence, a helicase binding sequence, a limiting structure, a first complementary sequence and a first primer sequence from the 5'end to the 3 'end in sequence, the limiting structure prevents helicase from moving, and the first chain is provided with a 3' free end; the second chain comprises a second complementary sequence and a restraint sequence or a sequence complementary with the nucleic acid sequence of the restraint sequence from the 5'end to the 3 'end in sequence, and the restraint sequence comprises a nucleic acid sequence of which the tail end is connected with a hydrophobic molecule; the first complementary sequence and the second complementary sequence are reversely complementary, and the sequencing linker is formed by annealing the first strand and the second strand. The sequencing linker and the sequencing linker compound are simple in construction process and high in yield.

The present invention relates to modified Dda helicases which can be used to control the movement of analytes such as polynucleotides. The modified Dda helicases are used in analyte detection and characterisation. The present invention also relates to novel protein pores and their uses in analyte detection and characterisation. The invention particularly relates to an isolated pore complex formed by a CsgG-like pore and a modified CsgF peptide, or a homologue or mutant thereof, thereby incorporating an additional channel constriction or reader head in the nanopore.

The invention provides an Auricularia auricula polysaccharide, its application and preparation method thereof, which belong to the technical field of improving polysaccharide. After being degreased, the Auricularia auricula is subjected to preliminary enzymolysis under the effect of helicase, is further subjected to deep enzymolysis under the effect of complex enzyme through synergetic ultrasound-assisted degradation and extraction with H2O2, and is subjected to mixed fermentation by Lactobacillus bulgaricus, Streptococcus thermophilus and Bifidobacterium longum, the obtained fermented Auricularia auricula polysaccharide is subjected to a phosphorylation reaction under the effect of a phosphorylation reagent, and after further deproteinization and decolorization, the obtained fermented Auricularia auricula polysaccharide is chelated with zinc salt to obtain a polysaccharide-zinc compound, and the amount of the extracted Auricularia auricula polysaccharide is improved. The finished product of the invention has the effects of reducing blood sugar and blood fat, regulating total cholesterol and effectively improving HDL cholesterol.

The invention discloses an imidazo [4, 5-b] pyridine compound capable of blocking mRNA translation of tumor cells and an application of the imidazo [4, 5-b] pyridine compound in preparation of antitumor drugs for blocking mRNA translation of tumor cells, and the imidazo [4, 5-b] pyridine compound has a structure shown in a formula (I) or a pharmaceutically acceptable salt of the imidazo [4, 5-b] pyridine compound. The mRNA translation of cancer promoting protein is crucial to the occurrence and development of malignant tumors, but a small molecular compound for targeted inhibition of mRNA translation is lacked clinically at present. The invention provides an imidazo [4, 5-b] pyridine compound, which can be combined with a translation initiation factor eIF4A and inhibit the ATP-dependent RNA helicase function of the translation initiation factor eIF4A so as to block the translation of mRNA and present proliferation inhibition and apoptosis promotion functions in various tumor cells. # imgabs0 #

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 invention belongs to the field of biomedicine and relates to a deuterated compound that inhibits the activity of the RNA helicase DHX33 and its synthesis method. It also relates to a pharmaceutical composition containing the compound and its use in the preparation of a drug for preventing and / or treating DHX33-related diseases. The structural formula of the deuterated compound is: #imgabs0#

The invention discloses a corn kernel development regulation gene ZmRH51 as well as an encoding protein, a functional marker and an application of the corn kernel development regulation gene ZmRH51. According to the application, a corn kernel mutant m223 is taken as a basic material, heterozygote of the corn kernel mutant m223 is hybridized with Zheng 58 (Z58) to construct an F2 segregation population, then phenotype identification and cytological observation are performed on the segregation population of the offspring, the gene ZmRH51 for controlling the mutation phenotype of the m223 is obtained through genetic analysis, BSR-seq analysis and map-based cloning, the gene is positioned in a nucleolus region, and the mutation phenotype of the m223 is controlled. The ZmRH51 is used for coding RNA helicase of a DEAD-Box gene family, and research shows that ZmRH51 participates in ribosome assembly and can influence processing of pre-rRNA in corn kernels; the excellent allelic variation genotype of the excavated ZmRH51 gene in the aspect of grain thickness is obtained through further excavation, the grain thickness and hundred-grain weight of the ZmRH51 gene can be increased through the utilization of the gene, and then the yield is increased. In addition, distribution and utilization potentials of different haplotypes in a selfing line are researched, and technical support and excellent germplasm resources are provided for utilization of the gene.

The invention provides a bifidobacterium animalis subspecies HX-BA21, and the preservation number of the bifidobacterium animalis subspecies HX-BA21 is CGMCC (China General Microbiological Culture Collection Center) NO.32958. The invention discloses bifidobacterium animalis subspecies HX-BA21 containing exosome metabiotics and an exosome-containing fermentation compound obtained by fermenting gastrodia elata through the HX-BA21. The fermentation compound comprises a probiotic protective layer (a core layer), an exosome delivery layer (a shell layer) and a prebiotics sustained release layer (a cocoon layer) from inside to outside. The probiotic protection layer comprises a sodium alginate-milk fat globule membrane compound and animal bifidobacterium subsp.animalis; the exosome delivery layer comprises a gelatin-chitosan compound and a gastrodia elata and probiotic mixed exosome; the prebiotic sustained-release layer comprises an octenyl succinic anhydride starch / polyvinyl alcohol compound and inulin. The compound can start cell repair by improving the cell migration rate, up-regulate DNA helicase and telomere related gene expression, delay premature senescence and delay cell senescence caused by D-galactose by adjusting the oxidative stress level.

The invention relates to a new method of characterising a target polynucleotide. The method uses a pore and a Dda helicase. The helicase controls the movement of the target polynucleotide through the pore. The invention also relates to modified Dda helicases which can be used to control the movement of polynucleotides and are particularly useful for sequencing polynucleotides.

The invention discloses a corynebacterium glutamicum whole genome random mutation tool and application thereof, and belongs to the technical field of genetic engineering and biological mutagenesis. DsDNA is unwound in the transcription process based on DNA helicase, DNA adenine deaminase and the DNA helicase are fused, and whole-genome random mutation of corynebacterium glutamicum is achieved. The whole genome random mutation method disclosed by the invention is applied to mutagenesis of an original strain of Corynebacterium glutamicum ATCC 13032, and a mutant strain of which the biomass is 1.95 times of that of WT (OD600 is 2.2) and 1.99 times of that of WT / pXMJ19 (OD600 is 2.16) when being cultured under the condition that the pH value is 5.5 is obtained. The corynebacterium glutamicum whole genome random mutation method disclosed by the invention has important guiding significance for screening other mutation strains with enhanced robustness.

The protein complex comprises cytidine deaminase and helicase. In some embodiments, the cytidine deaminase is an altered cytidine deaminase. In some embodiments, the protein complexes convert 5 methylcytosine to thymine. Kits, compositions, and methods of use comprising the protein complexes of cytidine deaminase and helicase are also described.

The invention discloses helicase ToPif 1, a preparation method of the helicase ToPif 1 and application of the helicase ToPif 1 in high-throughput sequencing. The amino acid sequence of the ToPif 1 helicase mutant is as shown in SEQ ID NO. 1. The helicase can be used for control and characterization of nucleic acid and applied to nanopore sequencing.

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.

A method for moving a polynucleotide through a transmembrane pore, comprising: under the control of an electric field force, moving a polynucleotide, which is linked to a helicase variant, through a transmembrane pore, wherein the helicase variant does not have active unwinding activity or translocation activity.

The invention discloses a spiro derivative serving as a WRN helicase inhibitor and application of the spiro derivative. The spiro derivative has better WRN helicase inhibitory activity, can be used for inhibiting growth of microsatellite unstable (MSI) tumor cells by inhibiting high-level DNA double-strand breakage (DSB) in microsatellite unstable (MSI) cells caused by WRN, is used for preventing and / or treating related cancers, especially colorectal cancer, gastric cancer, ovarian cancer, endometrial tumor and the like, and has a good application prospect. The vacancy of specific MSI type cancer targeting drugs can be filled, and the application prospect and value in the field of medicines are very good.

The present invention provides a modified ToPif1 helicase and its application, belonging to the field of gene sequencing technology. The modified ToPif1 helicase has SEQ ID NO:14 as the parent sequence, with at least one covalent bond between 221-229 and 401-405, and the amino acid numbering is based on SEQ ID NO:15. The modified ToPif1 helicase of the present invention can control the smooth movement of polynucleotides through the nanopore, reducing slippage or irregular movement.

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 invention discloses application of ATP-dependent DNA helicase RECG in improvement of agronomic traits of gramineous crops, corn overexpression helicase RECG or enhancement of enzyme activity can improve grain yield and plant biomass, and the application is of great significance to cultivation of new high-yield corn varieties.

Disclosed herein are compounds that can degrade lymphoid-specific helicase (HELLS) protein. Also disclosed herein are pharmaceutical compositions comprising the compounds, and methods of using the compounds, e.g., in the treatment of proliferative diseases such as cancers.

The invention discloses a sequencing linker, a sequencing linker compound, a method for multiple amplification of a target nucleic acid sequence and a nanopore sequencing method. Wherein the sequencing linker comprises a first chain and a second chain, the first chain comprises a sequencing guide sequence, a helicase binding sequence, a limiting structure, a first complementary sequence and a first primer sequence from the 5'end to the 3 'end in sequence, the limiting structure prevents helicase from moving, and the first chain is provided with a 3' free end; the second chain comprises a second complementary sequence and a restraint sequence or a sequence complementary with the nucleic acid sequence of the restraint sequence from the 5'end to the 3 'end in sequence, and the restraint sequence comprises a nucleic acid sequence of which the tail end is connected with a hydrophobic molecule; the first complementary sequence and the second complementary sequence are reversely complementary, and the sequencing linker is formed by annealing a first chain and a second chain; the sequencing linker further comprises a structure for preventing the second strand from being replaced by the polymerase. The sequencing linker and the sequencing linker compound are simple in construction process and high in yield.

Provided are compounds of the Formula (I):or pharmaceutically acceptable salts thereof, which are useful for the inhibition of DHX9 and in the treatment of a variety of DHX9 mediated conditions or diseases, such as cancer.

This application relates to the technical field of biomarkers, and particularly to a preparation method and application of an RNA vector-related translocation complex; the translocation complex includes an RNA vector, and the RNA vector includes an RNA vector core sequence, a biotin-labeled primer, and a digoxigenin-labeled primer. The forward sequence of the RNA vector core sequence is shown in SEQ ID NO.1, and the reverse sequence of the RNA vector core sequence is shown in SEQ ID NO.2; through the RNA vector including the RNA vector core sequence, the biotin-labeled primer, and the digoxigenin-labeled primer, one end of the RNA vector is connected to streptomycin-coated magnetic beads through the biotin-labeled primer, and the other end is connected to the digoxigenin-treated glass surface, with firm binding. The RNA vector core region can form a translocation complex with the Holo-RdRp polymerase and the nsp13 helicase, and the single-molecule magnetic tweezer technology can effectively reflect the kinetic characteristics of the nsp13 reaction in real time.

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.

Inhibitors of Werner syndrome helicase are provided, including compounds of Formulas J, I, II, III, IIIa, IIIa-1, and IIIa-2, pharmaceutical compositions thereof, and methods of treating cancer.

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.

Disclosed herein are certain helicase bicycle amides 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.