3 results about "Substrate analog" patented technology

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 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.