5 results about "Substrate analog" patented technology

The invention belongs to the technical field of sepsis treatment, and particularly relates to application of a preparation for preventing ENO1 from playing a glycolysis role in preparing a medicine for treating sepsis. It is found for the first time that promotion of interaction of IL1R2-ENO1 can inhibit the glycolysis level of macrophages, significantly inhibit pyroptosis of macrophages induced by LPS + ATP, inhibit generation of inflammatory mediators IL1beta and the like, relieve dysfunction of multiple organs and significantly improve the survival rate of mice, and it is also found that AP-III-a4 is a non-substrate analogue inhibitor of ENO1 and can inhibit the glycolysis ability of ENO1 after being combined with ENO1. Therefore, IL1R2 and AP-III-a4 can be used as a promising treatment target for treating sepsis when being used for preventing the ENO1 from playing a glycolysis role.

The application relates to the technical field of the cross of protein engineering and computational biology, and discloses a uracil-DNA glycosylase de novo design method based on physical priori and deep learning. A fixed function motif containing a catalytic core layer, a DNA binding interface layer and a structural support layer is extracted, and the fixed function motif and a substrate analog are used as geometric constraints; a full-atom diffusion model is used to generate a new protein topological skeleton; iteration optimization is carried out through deep learning sequence generation and physical force field refinement; sub-Angstrom level precision control of an active pocket and sequence-structure self-consistency are realized; finally, multi-dimensional screening is carried out by using an orthogonal prediction model and a Pareto optimal strategy. The application can break through the natural evolution limit, obtain a de novo designed UNG which is unique in sequence, has a sub-Angstrom level precision catalytic pocket and is compact in structure, and provide a new computational design strategy for the development of programmable gene editing tool enzymes.

The invention provides a gamma-lactam podophyllotoxin compound as well as a preparation method and application thereof, and belongs to the technical field of bioengineering. A series of podophyllotoxin analogues with new skeletons are finally obtained by chemically synthesizing a series of lactam ring substituted lactonic ring substrate analogues and combining in-vitro protein catalytic activity tests, and a new method of gamma-lactam podophyllotoxin analogues is successfully developed. According to the present invention, the ShDS protein is adopted as the catalyst, such that the substrate selectivity is high, the reaction condition is mild, the other functional groups are not affected while the specific reaction is catalyzed so as to easily protect the sensitive functional groups in the drug molecule, avoid the damage to the drug molecule, and reduce the generation of the side reaction and the consumption of the energy and the resource. The ShDS protein serving as a catalyst can catalyze multiple reaction cycles, the cost of the synthesis process is reduced, no harmful chemical reagent is used in the method, environmental pollution and waste generation can be effectively reduced, and the method conforms to the green chemistry principle.

The present specification provides a pharmaceutical composition for preventing or treating gastric cancer, comprising, as an active ingredient, a protein activity inhibitor or gene expression inhibitor for at least one of SHMT1, TYMS, MTHFD1, and DHFR, wherein the protein activity inhibitor is at least one of a compound, a peptide, a peptidomimetic, a substrate analog, an aptamer, and an antibody that specifically bind to a protein, and the gene expression inhibitor is at least one of an antisense nucleotide, RNAi, siRNA, miRNA, shRNA, and a ribozyme that complementarily bind to mRNA of a gene.

This invention discloses terpenoid compounds with anticancer activity and their preparation methods, belonging to the field of biotechnology. The invention employs a chemical-enzymatic method, first chemically synthesizing the natural substrate analog 7-O-FPP, and then using the sesquiterpene synthase TmS for in vitro catalysis to obtain three oxygen-containing sesquiterpene products. MTT activity assays showed that the three compounds exhibited significant anticancer activity against gastric cancer SGC7901, lung cancer NCI-H1975, cervical cancer HeLa, and esophageal squamous cell carcinoma KYSE-150 cells. Compounds 1 and 3 showed anticancer activity against various cancer cell lines. 50 The concentration of compounds below 1 μg / mL showed significantly superior activity compared to the clinical drug β-elemene; compound 2 exhibited higher activity against lung cancer cells and low toxicity to normal MRC-5 cells. This invention provides an efficient method for preparing novel terpenoid compounds, and the resulting compounds offer high-quality lead molecules for the development of new anticancer drugs, demonstrating promising application prospects.