35 results about "20s proteasome" patented technology

Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsinlike activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.

Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include at least three peptide units, an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.

Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include at least three peptide units, an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.

The invention discloses a polypeptide inhibitor having an efficient and specific inhibiting effect for the functions of REG gamma-20S proteasome. The main technical scheme is as follows: the phosphorylation/dephosphorylation modification of NIP30 is a 'molecular switch' for regulating the REG gamma-proteasome, namely, the phosphorylation modification of four sites including NIP30S226, S227, S228 and S230 has great importance for the binding of NIP30 and REG gamma and the degradation for the REG gamma substrate. According to the technical scheme, the polypeptide inhibitor is designed and synthesized based on the phosphorylation modification for the binding of NIP30 and REG gamma, and the polypeptide inhibitor can efficiently and specifically block the functions of the REG gamma-20S proteasome. Compared with the existing chemical inhibitor, the polypeptide inhibitor for the REG gamma-proteasome disclosed by the invention has the advantages of high efficiency and low toxicity, and a noveltreatment target and means are expected to be provided for the malignant tumor (such as metastatic tumor of bone with unknown primary lesion) due to overexpression of REG gamma.

The invention discloses a construction method of a Psm3 conditional gene knockout mouse model and application of the Psm3 conditional gene knockout mouse model. According to the construction method, the third exon to the fifth exon of the Psm3 gene are knocked out by using a Cas9/RNA system gene targeting technology, so that inactivation of the whole gene is realized, and the Psm3 gene conditional knockout mouse model is obtained. The Psme3 is used as a proteasome activating factor to regulate the hydrolytic activity of 20S proteasome and regulate and control the degradation of various tumor-related factors. The Psm3 gene conditional knockout mouse model constructed by the invention lays a foundation for further research on biological functions of the Psm3 gene, and can provide an ideal model for an action mechanism in occurrence and development of solid tumors with high expression of Psm3.

The present invention relates in a first aspect to a method for the purification of biological macromolecular complexes. Typically, no chromatography steps are applied. That is, the present invention relates to a method for the purification of biological macromolecular complexes Furthermore, the present invention relates to a method for crystallization of biological macromolecular complexes comprising the step of purification as described followed by crystallization in a reservoir solution containing a water-soluble polymer. Furthermore, purified biological macromolecular complexes obtainable by the method according to the present invention are provided as well as crystallized biological macromolecular complexes. Finally, a method for determining the suitability of a candidate compound for inhibiting the 20S proteasome of an individual is provided. Said method is particularly useful in personalized medicine identifying suitable inhibitors of the 20S proteasome in individuals for treating, ameliorating or preventing a cancer, an autoimmune disease, a muscular dystrophy, emphysema or cachexia accompanying cancer or AIDS.