39 results about "Dna binding activity" patented technology

The present invention relates to an Argonaute protein mutant which lacks DNA cleavage activity, but has DNA binding activity. The mutation of the mutant is located in a PIWI domain. The invention alsorelates to application of the protein mutant particularly in the enrichment of target DNA and in the construction of a sequencing library. Therefore, the present invention also relates to a method for enriching the target DNA. The method comprises the steps of: (a) designing a leader sequence for a specific sequence in the target DNA; (b) combining the mutant, the leader sequence and the target DNA according to the present invention to obtain a mutant-leader sequence-target DNA ternary complex; (c) capturing the mutant-leader sequence-target DNA ternary complex through a capture medium; and (d) isolating the target DNA from the captured mutant-leader sequence-target DNA ternary complex to obtain enriched target DNA.

The present invention provides novel compounds, corresponding to formulae I and II, respectively, which are able to reactivate the apoptosis-inducing function of mutant p53 proteins. This reactivation is provided by restoration of sequence-specific DNA-binding activity and transcriptional transactivation function to mutant p53 proteins, and modulation of the conformation-dependent epitopes of the p53 protein. Accordingly, the substances according to the invention will be used in pharmaceutical compositions and methods for treatment of patients suffering from various types of tumors.

Malignant melanoma cells spontaneously generate reactive oxygen species (ROS) that promote constitutive activation of the transcription factor nuclear factor-kB (NF-kB). Although antioxidants and inhibitors of NAD(P)H oxidases significantly reduce constitutive NF-kB activation and suppress cell proliferation, the nature of the enzyme responsible for ROS production in melanoma cells has not been determined. To address this issue, we now have characterized the source of ROS production in melanoma cells. ROS are generated by isolated, cytosol-free melanoma plasma membranes, with inhibition by NAD(P)H oxidase inhibitors. The p22phox, gp91phox and p67phox components of the human phagocyte NAD(P)H oxidase, and the 91phox homolog NOX4 were demon-strated in melanomas by RT-PCR and sequencing, and protein product for both p22phox and gp91phox were detected in cell membranes by immunoassay. Normal human epidermal melanocytes expressed only p22phox and NOX4. Melanoma proliferation was reduced by NAD(P)H oxidase inhibitors and by transfection of antisense but not sense oligonucleotides for p22phox and NOX4. Also, the flavoprotein inhibitor diphenylene iodonium inhibited constitutive DNA binding of nuclear protein to the NF-kB and cyclic-AMP response element consensus oligonucleotides, without affecting DNA binding activity to AP-1 or OCT-1.

Recently, the development of inducible expression systems has involved exploitation of the p-cym operon from Pseudomonas putida. Disclosed herein are novel expression systems and components thereof, which involve the development of CymR variants with reverse DNA binding activity, such that they exhibit increased affinity for DNA in a presence rather than an absence of an effector molecule such as cumene or an equivalent thereof. Also disclosed are the CymR variants, fusion proteins incorporating such variants, and their use in the control and expression of polynucleotides.

Recently, the development of inducible expression systems has involved exploitation of the p-cym operon from Pseudomonas putida. Disclosed herein are novel expression systems and components thereof, which involve the development of a CymR variant with reverse DNA binding activity, such that they exhibit increased affinity for DNA in a presence rather than an absence of an effector molecule such as cumene or an equivalent thereof. Also disclosed are the CymR variant, fusion proteins incorporating such a variant, and its use in the control and expression of polynucleotides. The CymR variant comprises a 142Glu to 142Gly single point mutation of wild type CymR.

The present invention provides novel compounds, corresponding to formulae I and II, respectively, which are able to reactivate the apoptosis-inducing function of mutant p53 proteins. This reactivation is provided by restoration of sequence-specific DNA-binding activity and transcriptional transactivation function to mutant p53 proteins, and modulation of the conformation-dependent epitopes of the p53 protein. Accordingly, the substances according to the invention will be used in pharmaceutical compositions and methods for treatment of patients suffering from various types of tumours.

An epigenetic regulatory polypeptide complex comprises at least a first domain having site-specific DNA binding activity and at least a second domain having an arginine methyltransferase activity, wherein the second domain is capable of methylating an arginine residue located in the tail region of a histone H2A. The complex is able to regulate gene expression in cells, particularly in mammalian stem cells by controlling the methylation of R3 in the tail regions of histones H2A and H4. The complex is exemplified by a polypeptide complex comprising the DNA binding activity of Blimpi and the arginine methyltransferase activity of Prmt5.

The present disclosure relates to an anticancer use of a novel compound, i.e., 2-methoxy-4-(3-(4-methoxyphenyl)propyl-1-en-1-yl)phenol. The compound of the present disclosure effectively inhibits the growth of cancer cells and tumors in vitro and in a xenograft animal model. The compound of the present disclosure illustrates an anticancer activity by inhibiting a DNA binding activity of transcription factor STAT 3 in cancer cells, inducing apoptosis of cancer cells, and reducing the expression of a cell cycle regulatory protein. The compound of the present disclosure can be developed as an active ingredient of a strong anticancer drug.

Disclosed are novel methods for the therapeutic treatment of cancer and angiogenesis. The enzyme Ape1 / Ref-1, via its redox function, enhances the DNA binding activity of transcription factors that are associated with the progression of cancer. The present disclosure describes the use of agents to selectively inhibit the redox function of Ape1 / Ref-1 and thereby reduce tumor cell growth, survival, migration and metastasis. In addition, Ape1 / Ref-1 inhibitory activity is shown to augment the therapeutic effects of other therapeutics and protect normal cells against toxicity. Further, Ape1 / Ref-1 inhibition is shown to decrease angiogenesis, for use in the treatment of cancer as well other pathologic conditions of which altered angiogenesis is a component.

Thermostable DNA ligases with enhanced DNA binding activity and reaction activity are obtained. These modified thermostable DNA ligases having enhanced DNA binding activity compared to the wild type can be obtained by substituting a negatively charged amino acid (for example, the amino acid corresponding to the aspartic acid at position 540 of SEQ ID NO: 1) present at the N-terminal side of the C-terminal helix moiety of thermostable DNA ligases from thermophilic bacteria, hyperthermophilic bacteria, thermophilic archaea, or hyperthermophilic archaea, with a non-negatively charged amino acid (for example, alanine, serine, arginine, or lysine).

A method of isolating at least one phenanthroindolizidine alkaloid, in particular with telomerase inhibitory activity, from Tylophora atrofolliculata is used to isolate and obtain for example about six to eight phenanthroindolizidine alkaloids, including at least four new phenanthroindolizidine alkaloids which have not been previously isolated. Experimental tests confirmed an exceptional telomerase inhibitory activity of the phenanthroindolizidine alkaloids isolated. A pharmaceutical composition includes at least one phenanthroindolizidine alkaloid and at least one pharmaceutical tolerable excipient. Still further, a method of treating a subject suffering from cancer includes administering at least one phenanthroindolizidine alkaloid isolated from Tylophora atrofolliculata. Also, a method of treating a subject suffering from cancer includes administering to the subject at least one phenanthroindolizidine alkaloid having certain formula.

The invention discloses a core structural domain of VirB protein, and coding genes and applications thereof. The invention provides VirB core segments or fusion proteins containing the VirB core segments; the VirB core segments are described as (a) or (b). (a) a protein composed of amino acid residues from the 22nd site to the 143rd site in the sequence table sequence No.1; (b) proteins which are derived from the proteins of (a), wherein one or a plurality of amino acid residues are substituted and / or lost and / or added, and the proteins of (b) possess DNA binding activity. The invention also discloses the applications of the VirB core segments or the fusion proteins in preparation of products used for binding with DNA, and in preparation of products used for identifying DNA. The invention provides the core structural domain of VirB protein, and operating principles of VirB protein are revealed at the molecular level, so that accurate and all-around structural biology information is provided for the design of structure oriented drugs.

Compounds comprising a metal complex having the structure [X—Y—Z-Mn+]p+.B are disclosed in which X is a histone deacetylase inhibitor, Mn+ is a DNA-binding heavy metal ion, Y is an aliphatic or aromatic spacer or is absent, and Z is a mono- or bi-dentate or chelating donor linker, or a bridging linker, P+ designates the charge on the complex ion, which may be positive, negative or absent and B is a counterion or is absent. The linker Z is labile and its metal complex X—Y—Z-Mn+ is capable of being hydrolysed in-vivo. The compounds find application in the treatment of cancer.