40 results about "SH3 domain" patented technology

The present invention relates to a recombinant binding protein comprising at least one derivative of the Src homology 3 domain (SH3) of the FYN kinase, wherein at least one amino acid in or positioned up to two amino acids adjacent to the src loop and/or at least one amino acid in or positioned up to two amino acids adjacent to the RT loop is substituted, deleted or added. Furthermore, the invention is directed to fusion proteins comprising a binding protein according to the invention fused to a pharmaceutically and/or diagnostically active component. In addition, the invention concerns nucleotides coding for these binding and/or fusion proteins as well as corresponding vectors and host cells. Last but not least, the present invention relates to the use of binding and/or fusion proteins of the present invention for preparing a medicament or a diagnostic means as well as to pharmaceutical or diagnostic compositions comprising said binding and/or fusion proteins.

Peptides having general and specific binding affinities for the Src homology region 3 (SH3) domains of proteins are disclosed in the present invention. In particular, SH3 binding peptides have been isolated from phage-displayed random peptide libraries which had been screened for isolates that bind to bacterial fusion proteins having an SH3 domain and glutathione S-transferase (GST). Preferred peptides are disclosed which comprise a core 7-mer sequence (preferably, a consensus motif) and two or more, preferably at least six, additional amino acid residues flanking the core sequence, for a total length of 9, preferably at least 13, amino acid residues and no more than about 45 amino acid residues. Such peptides manifest preferential binding affinities for certain SH3 domains. The preferred peptides exhibit specific binding affinities for the Src-family of proteins. In vitro and in vivo results are presented which demonstrate the biochemical activity of such peptides.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a central signaling enzyme in a cell nucleus. PARP-1 is a target for the development of radio and chemo sensitizing agents in cancer treatment as well as providing protection from stroke. An SH3 domain and an SH3 ligand domain have now been discovered on the PARP-1 protein. These domains are involved in PARP-1 activation. This discovery makes possible the use of bioinformatics tools for the design of new drugs and strategies for drug target selection, specifically targeting the PARP-1 enzyme.

Disclosed is a composition of matter involving a recombinant fusion protein comprising a a pharmacologically active protein partner, and a small pharmacologically inactive protein domain partner of human origin, such as but not limited to, a 10^th fibronectin III domain, a SH3 domain, a SH2 domain, a CH2 domain of IgG1, a PDZ domain, a thrombospondin repeat domain, an ubiquitin domain, a leucine-rich repeat domain, a villin headpiece HP35 domain, a villin headpiece HP76 domain, or a fragment or modification of any of these. Also disclosed are nucleic acids (e.g., DNA constructs) encoding the fusion protein, expression vectors and recombinant host cells for expression of the fusion protein, and pharmaceutical compositions containing the recombinant fusion protein and a pharmaceutically acceptable carrier, and method of producing a pharmacologically active recombinant fusion protein.

A purified polypeptide includes an NADPH oxidase cytosolic cofactor polypeptide NOXA1 or P67^phox having a C-terminal SH3 domain insertion mutation of at least three consecutive amino acids positioned between PEDL and GIFPK motifs of said SH3 domain so as to reduce activity of the purified polypeptide relative to the wild-type cofactor polypeptide. A process for treating, inhibiting, or prophylatically preventing a disease associated with the overproduction of reactive oxygen species involving NOXn where n is 1-4 inclusive includes the administration of a therapeutically effective amount with a purified polypeptide to a subject tissue that is overproducing reactive oxygen species through a NOXn pathway.

This invention provides a new in vitro screening method for the detection of protein-protein and other interactions. The method has been developed and applied to a commercial cDNA library to search for novel protein-protein interactions. PDZ, WW and SH3 domains from PSD95, Nedd4, Src, Abl and Crk proteins were used as test targets. 12 novel putative and 2 previously reported interactions were identified for 6 protein interaction modules in test screens. The novel screening format, dubbed TAIS (target-assisted iterative screening), provides an alternative platform to existing technologies for a pair-wise characterization of protein-protein, and other, interactions.

The present invention provides SH3 domain binding inhibitors comprising, as an active ingredient, a non-peptide compound exhibiting SH3 domain binding inhibitory activity, a low molecular weight compound with molecular weight less than 750 which exhibit SH3 domain binding inhibitory activity, in particular, a compound represented by the general formula (I) or (II) described above, a cytochalsin, etc., or pharmaceutically acceptable salts thereof. The present invention also provides compounds represented by the general formula (Va), (Vb) or (VI) described above or pharmaceutically acceptable salts thereof.

The present invention provides application of urine SH3 domain glutamic acid-rich-like protein 3 protein (SH3 domain-binding glutamic acid-rich-like protein 3 protein, SH3BGRL3, also known as SH3 domain-binding protein 1) and polypeptide fragments thereof, and specifically provides application of the urine SH3 domain glutamic acid-rich-like protein 3 protein and the polypeptide fragments thereof in preparation of a preparation for detecting and assisting diagnosis of lung adenocarcinoma. Researches confirm that compared with normal control and a lung adenocarcinoma patient group, different polypeptide fragments of the SH3 domain glutamic acid-rich-like protein 3 protein are expressed in the urine of a patient with the lung adenocarcinoma, and can be used for the detecting and assisting diagnosis of the lung adenocarcinoma The advantages of non-invasive acquisition, large-scale repeated sampling, and convenient storage of a urine sample can be played. The urine sample is used to detectthe SH3 domain glutamic acid-rich-like protein 3 protein and the polypeptide fragments thereof.

The present invention relates to a method for the production of a library comprising recombinant derivatives of the SH3 domain of the Fyn kinase of SEQ ID NO: 1 as well as a method for selecting from a library comprising recombinant derivatives of the SH3 domain of the Fyn kinase of SEQ ID NO: 1 one or more of said derivatives having a specific binding affinity to a protein or peptide.

The present invention describes a newly discovered full-length polynucleotide encoding an SH2/SH3 domain-containing adapter protein, called hSLAP-2, cloned, isolated and identified. Also described are the hSLAP-2 polypeptide sequence, expression vectors, host cells, agonists, antagonists, anti-sense molecules, and antibodies related to the polynucleotide and/or polypeptide of the present invention. Methods for screening for modulators, particularly inhibitors, of the hSLAP-2 protein and use of the hSLAP-2 polynucleotide and polypeptide for therapeutics and diagnostics are described.

The invention relates to an Eps8-SH3 structural domain-based dual antitumor polypeptide. The polypeptide has an amino acid sequence of Lys-Tyr-Ala-Lys-Ser-Lys-Tyr-Asp-Phe (SEQ ID No: 1). The dual antitumor polypeptide can induce cytotoxic T cells, effectively kill HLA-A*2402 positive and Eps8 positive tumors, directly inhibit HLA-A*2402 positive and Eps8 positive tumor cell proliferation and be used for preparation of dual antitumor drugs.

A method of identifying a lead or candidate compound that modulates the activity of GTPase-Activating Protein SH3 Domain-Binding Proteins (G3BP) is provided, which includes determining whether a compound modulates the interaction between the N-terminal Nuclear Transport Factor 2-like (NTF2L) domain of G3BP and FGDF peptide of ubiquitin specific protease 10 (USP10) or non-structural protein 3 (nsP3).

The invention provides a reagent of a marker composition capable of detecting gestational hypertension associated diseases. The marker composition is prepared from glutamate-rich SH3 domain binding protein 3, plasma protease inhibitory protein C1, relaxin, serine protease inhibitory protein A5, clusterin, serine protease inhibitory protein A4, serine protease peptidase inhibitory protein C1, phosphatidylinositol-glycan biosynthesis type F protein, pregnancy-associated plasma protein, insulin-like growth factors, calnexin and attractin. The accuracy rate of the marker composition provided by the invention for detecting gestational hypertension is 98% which meets the requirement for clinical disease screening and can not be realized by the existing gestational hypertension detection technology.

The invention discloses a function and application of SH3 domain-containing RING finger protein 2 (Sh3rf2) in preparing drugs for treating a non-alcoholic fatty liver disease and/or type-2 diabetes. According to the function and the application, Sh3rf2 gene knockout mice and wild type C57 mice are taken as experiment objects, through a fat mice model induced with high-fat and high-cholesterol (HFHC) diet, it is found that the weight of Sh3rf2 gene knockout mice increases in comparison with that of the wild type C57 mice in a control group; results of the liver weight, the liver/body weight, lipid composition pathological staining and the like all indicate that the Sh3rf2-KO mice in an HFHC group have obviously serious lesion of the fatty liver, and lipid accumulation increases; and the results show that Sh3rf2 gene knockout significantly worsens the progression of the non-alcoholic fatty liver disease. In allusion to the effect of the Sh3rf2, the Sh3rf2 can be used for preparing the drugs for preventing, alleviating and / or treating the nonalcoholic fatty liver disease and/or the type-2 diabetes.

The present invention relates to a composition comprising an inhibitor of the expression or activity of SH3 domain containing ring finger 2 (SH3RF2) for preventing or treating cancers. More specifically, since the SH3RF2 protein, of which the expression level increases in various cancer tissues, binds to PAK4, which is a cancer-associated gene, to regulate an apoptosis inhibitory function of the PAK4 protein by ubiquitination activity of SH3RF2 RING domain, cancer cells, in which the expression of SH3RF2 is inhibited, sensitively respond to the induction of apoptosis to promote apoptosis and reduce in vivo tumorigenicity, such that the inhibitor of the expression or activity of SHRF2 can be useful as a composition for preventing or treating cancers.

Provided are compounds that bind to SH3 domains. Also provided are combinatorial libraries for discovering such compounds. Methods of identifying a compound that binds to an SH3 domain are also provided. Methods of inhibiting an activity of a protein comprising an SH3 domain are additionally provided. Additionally provided are methods of inhibiting the activity of a protein comprising an SH3 domain and methods of treating a mammal having a deleterious condition that is mediated by a protein comprising an SH3 domain. The use of a compound that binds to the SH3 domain of a protein kinase in the manufacture of a medicament for the treatment of a deleterious condition in a mammal that is dependent on a protein kinase for induction or severity are also provided.

The present invention describes a newly discovered full-length polynucleotide encoding an SH2/SH3 domain-containing adapter protein, called hSLAP-2, cloned, isolated and identified. Also described are the hSLAP-2 polypeptide sequence, expression vectors, host cells, agonists, antagonists, anti-sense molecules, and antibodies related to the polynucleotide and/or polypeptide of the present invention. Methods for screening for modulators, particularly inhibitors, of the hSLAP-2 protein and use of the hSLAP-2 polynucleotide and polypeptide for therapeutics and diagnostics are described.

A nucleic acid molecule encoding a fusion protein composed of an inducible multimerization moiety at the amino terminus, and a GTPase-Activating Protein SH3 Domain-Binding Protein (G3BP) is provided for exogenous stimulus/G3BP-mediated stress granule formation. Further disclosed are chemical or light inducible multimerization proteins or protein domains that can be used for the nucleic acid molecule production, and a method of inducing stress granule formation in a cell comprising expressing the nucleic acid molecule.

The invention provides a reagent capable of detecting a hypertensive disorders in pregnancy associated marker composition. The marker composition comprises three or more of calnexin, attractin, clusterin, cytokeratin 18, pregnancy-specific beta-1-glycoprotein 4, SH3 domain-binding glutamic acid-rich-like protein 3, serine protease inhibitor A4, plasma serine protease inhibitor A5, serpin peptidaseinhibitor, clade C member 1, relaxin-3, APOC4, Annexin A1, and insulin-like growth factor-binding protein 2. The marker composition provided by the invention has gestational hypertension detection accuracy up to 90% or more meets the requirements of clinical disease screening, which are unachievable by the current gestational hypertension detection technology.

Peptides having general and specific binding affinities for the Src homology region 3 (SH3) domains of proteins are disclosed in the present invention. In particular, SH3 binding peptides have been isolated from three phage-displayed random peptide libraries which had been screened for isolates that bind to bacterial fusion proteins of SH3 domains and glutathione S-transferase (GST). Preferred peptides are disclosed having a core 7-mer sequence (preferably, a consensus motif) and two or more, preferably at least six, additional amino acid residues flanking the core sequence, for a total length of 9, preferably at least 13, amino acid residues and no more than about 45 amino acid residues. Such peptides manifest preferential binding affinities for certain SH3 domains. The preferred peptides exhibit specific binding affinities for the Src-family of proteins. In vitro and in vivo results are presented which demonstrate the biochemical activity of such peptides.