14 results about "Metallo enzyme" patented technology

The present disclosure provides a method for biocatalytic production of a polycyclic peptide comprising providing a peptide sequence containing a recognition motif for a radical S-adenosylmethionine metallocnzyme (SAM enzyme), exposing the peptide sequence to an enzymatic reaction including catalysis under standard enzymatic reaction conditions with the radical SAM enzyme, and generating a further cyclized peptide by modifying a product of the enzymatic reaction chemically and / or via enzymes. The radical SAM enzyme catalysis generates macrocyclic modifications using unactivated carbon centers. The product of the enzymatic reaction may be modified using haloalkane- or haloacetyl-containing compounds, macrocyclases, or additional radical SAM enzymes. The peptide sequence may be altered at permissive sites to generate libraries of polycyclic peptide structures. The enzymatic reaction may occur at ambient temperature and pH under buffered aqueous conditions.

Provided are a method for preparing a metalloenzyme inhibitor compound 1-cyclopropyl-2-(6-(difluoromethyl)pyridazin-4-yl)-5,6-difluoro-1H-benzo[d]imidazole, and an important intermediate for preparing the compound.

The invention belongs to the field of computer-aided drug design, and discloses a metal binding group extraction method based on chemical informatics analysis and modeling. The method comprises the following steps: constructing a metal binding compound data set; training and optimizing a metal combined compound prediction model by using a decision tree-based model and a graph neural network algorithm; using an SHAP interpretable method to analyze a relationship between the key features and a prediction result, and deriving a structure fragment with potential metal binding capacity; according to the attention score of the Attentive FP model, an atomic weight heat map of molecules in the test set is drawn, and key metal binding fragments are determined; molecules in the training set are fragmented, and representative substructures are extracted; a metal binding fragment chemistry library is compiled. According to the method, the problem that metal binding group extraction is limited to a compound structure data set is solved, efficient extraction of any metal ion binding group is realized, and discovery and research of metalloenzyme-related drugs are accelerated.

The pharmaceutical compounds have anti-inflammatory activity and, in some embodiments, can function as metalloenzyme inhibitors for beneficial modulation of metalloproteins. The pharmaceutical compositions can include a therapeutically effective amount of the compound and a pharmaceutically acceptable vehicle. The pharmaceutical compositions can be useful for treating disorders associated with chronic inflammation and / or misregulation of metalloenzymes, including hemochromatosis, cancers such as breast cancer, or neurodegenerative diseases such as Alzheimer's disease.

Discovery of the first rare earth-dependent enzyme in methylotrophic M. extorquens AM1 prompted research toward understanding the unique chemistry at play in these systems. This enzyme, an alcohol dehydrogenase (ADH), features a La3+ ion closely associated with redox-active coenzyme pyrroloquinoline quinone (PQQ). AM1 also produces a periplasmic PQQ-binding protein characterized by a Lys residue hydrogen-bonded to PQQ. Accordingly, we prepared K115A-, and K115D-PqqT variants to assess the relevance of this site toward metal binding. Isothermal titration calorimetry experiments, and titrations monitored by UV-vis absorption and emission spectroscopies support that K115D-PqqT binds tightly (Kd=0.6±0.2 μM) to La3+ in the presence of bound PQQ and produces spectral signatures consistent with those of ADH enzymes. Addition of benzyl alcohol to La3+-bound PQQ⊂K115D-PqqT produces spectroscopic changes associated with PQQ reduction, and chemical trapping experiments reveal the production of benzaldehyde, supporting ADH activity.

This application discloses the application of Fe / Mn bimetallic enzymes in the preparation of anti-periodontalgia or teeth whitening agents. The Fe / Mn bimetallic enzyme exhibits excellent photothermal properties and peroxidase-like activity; that is, under photothermal synergy, its POD-like activity can be significantly enhanced, generating more ·OH groups. In antibacterial coating experiments against *Porphyromonas gingivalis* and drug-resistant *Staphylococcus aureus*, Fe / Mn BA, through photothermal synergistic chemokinetic therapy, achieved antibacterial rates exceeding 90%. By treating periodontitis through anti-inflammatory and antibacterial action and achieving teeth whitening through pigment degradation, the application of this biatomic nanozyme provides a new research direction for the application of artificial enzymes in oral diseases and is expected to open up broader pathways to address the challenges currently faced by artificial enzyme antibacterial technologies.

The present invention provides a solid form of a metalloenzyme inhibitor compound 1-cyclopropyl-2-(6-(difluoromethyl)pyridazine-4-yl)-5,6-difluoro-1H-benzo[d]imidazole, and in particular to a crystal form and an amorphous solid form, and a preparation method for the compound, a pharmaceutical composition comprising the compound, and a use of the compound.

This invention discloses a method for improving the soluble expression of the large subunit of [NiFe] hydrogenase in *Escherichia coli*, belonging to the fields of protein engineering and industrial microbiology. This method involves fusing a short-chain solubilizing peptide XXA to the C-terminus of the target [NiFe] hydrogenase large subunit to form a fusion protein. This design significantly promotes the soluble expression of the target protein while preserving the accessibility of the C-terminal hydrolysis site, enabling it to transform from an inclusion body form to a soluble form under anaerobic high-density fermentation conditions. This invention overcomes the long-standing technical bias in the field that C-terminal fusion hinders the maturation and processing of [NiFe] hydrogenase, achieving a balance between solubilizing effect and processing compatibility. It provides a new technical pathway for the recombinant production of complex metalloenzymes and has significant application value in the industrial preparation of hydrogenase, basic enzymology research, and bioenergy.

The invention relates to the technical field of biological medicine, in particular to a biomarker combination, a kit of the biomarker combination and application of the biomarker combination in diagnosis of acute Stanford B-type aortic dissection (ATBAD). The biomarker combination comprises serum amyloid protein A1 (SAA1), serum amyloid protein A2 (SAA2), C-reactive protein (CRP), neutrophil elastinase (ELANE), matrix metalloenzyme 9 (MMP9), nest protein 1 (NID1), mannose binding lectin 2 (LMAN2) and proprotein convertase subtilisin / kexin type 9 (PCSK9), and the biomarker combination can realize high-sensitivity and high-accuracy detection of ATBAD. And the anti-interference capability is excellent.

Embodiments include metalloenzymes and methods for conducting a nitrogen migration reaction catalyzed by a metalloenzyme. Embodiments include metalloenzymes including one or more mutations. A method for forming a non-canonical amino acid includes catalyzing a nitrogen migration reaction to form a non-canonical amino acid using an azanyl moiety-containing substrate and a metalloenzyme catalyst.