21 results about "Norleucine" patented technology

The invention relates to an N-terminal acetylation and C-terminal ethylamine dual-modified LMN-NKA polypeptide derivative or a pharmaceutically acceptable salt and a preparation method thereof. The chemical name of the LMN-NKA polypeptide derivative is N-acetyl-L-aspartic acid-L-lysine-L-phenylalanine-L-valine-glycine-N-methyl-L-leucine-L-n-leucine-ethylamine, and the structural general formula of the LMN-NKA polypeptide derivative is Ac-Asp-Lys-Phe-Val-Gly-NMe-Leu-Nle-NHCH2 CH3, and the structural general formula of the LMN-NKA polypeptide derivative is shown in the description. According to the dual-modification strategy, the binding activity of the NK2 receptor can be specifically reserved, the enzymolysis stability is high, the transmembrane efficiency is high, the lipid solubility is high, and the physicochemical property is stable. The LMN-NKA polypeptide derivative or the pharmaceutically acceptable salt thereof disclosed by the invention is particularly suitable for preparing a medicine for treating diseases related to an NK2 receptor.

The invention discloses an antibacterial peptide, a pharmaceutical composition and application, and belongs to the field of polypeptide medicines.The antibacterial peptide forms a novel annular conformation by introducing n-leucine and 2-aminobutyric acid to construct a parent nucleus structure. The affinity of the antibacterial peptide to the main component phosphatidylglycerol of a bacterial cell membrane is remarkably improved, is improved by 31 times or more compared with polymyxin B and is improved by 16 times or more compared with D50 peptide, and the selectivity of the antibacterial peptide to the main component phosphatidylcholine of a mammalian cell membrane is improved by hundreds of times or more compared with that of a control peptide. The polymyxin B peptide has extremely low toxicity to HK-2 kidney cells, and the biological safety of the polymyxin B peptide is obviously superior to that of polymyxin B and D50 peptide. The minimum inhibitory concentration of the antibacterial peptide to gram-negative bacteria is as low as 0.03 mu g / mL, is about 33 times higher than that of polymyxin B, and is 17-33 times higher than that of D50 peptide. The treatment effect of the antibacterial peptide is obviously superior to that of polymyxin B and D50 peptide in various infection models, and the antibacterial peptide is expected to be developed into a novel anti-infection drug and is used for preventing and treating various infections.

This application provides a skin-renewing composition containing an acid-enzyme peptide, comprising lactobionic acid, hexanoyl dipeptide-3-leucine, and papain; the mass ratio of lactobionic acid, hexanoyl dipeptide-3-leucine, and papain is 0.1~15:0.5~15:0.05~5. This application also provides a product comprising the above composition and its application. This application combines lactobionic acid, papain, and hexanoyl dipeptide-3-leucine for biological skin renewal, i.e., exfoliation. The three components interact synergistically, significantly increasing the content of exfoliated keratin proteins and providing excellent exfoliation effects. Furthermore, the composition provided in this application has low irritation.

Prodrugs of glutamine analogs are disclosed, such as the prodrugs of aza-serine and 6-diazo-5-oxo-norleucine (DON) and 5-diazo-4-oxo-L-norvaline (L-DONV).

The present invention relates to methods and compositions for preventing erroneous incorporation of n-leucine into a protein during the production of a recombinant protein in a bacterium. The invention also provides microbial host cells and nucleic acid molecules for use in the methods and compositions provided herein.

The invention provides a skin care composition containing acid enzyme peptide. The skin care composition comprises lactobionic acid, hexanoyl dipeptide-3-n-leucine and papain, the mass ratio of the lactobionic acid to the hexanoyl dipeptide-3-n-leucine to the papain is (0.1 to 15) to (0.5 to 15) to (0.05 to 5). The invention further provides a product containing the composition and application of the product. According to the invention, lactobionic acid, papain and hexanoyl dipeptide-3-n-leucine are compounded for use, when the composition is used for biological skin renewal, namely exfoliating, the three components interact with each other and have a synergistic effect, the content of eluted keratin can be remarkably increased, and the composition has a good exfoliating effect. In addition, the composition provided by the invention is relatively low in irritation.

The invention discloses an antibacterial peptide, a pharmaceutical composition and application, and belongs to the field of polypeptide medicines.The antibacterial peptide forms a novel annular conformation by introducing n-leucine and 2-aminobutyric acid to construct a parent nucleus structure. The affinity of the antibacterial peptide to the main component phosphatidylglycerol of a bacterial cell membrane is remarkably improved, is improved by 31 times or more compared with polymyxin B and is improved by 16 times or more compared with D50 peptide, and the selectivity of the antibacterial peptide to the main component phosphatidylcholine of a mammalian cell membrane is improved by hundreds of times or more compared with that of a control peptide. The polymyxin B peptide has extremely low toxicity to HK-2 kidney cells, and the biological safety of the polymyxin B peptide is obviously superior to that of polymyxin B and D50 peptide. The minimum inhibitory concentration of the antibacterial peptide to gram-negative bacteria is as low as 0.03 mu g / mL, is about 33 times higher than that of polymyxin B, and is 17-33 times higher than that of D50 peptide. The treatment effect of the antibacterial peptide is obviously superior to that of polymyxin B and D50 peptide in various infection models, and the antibacterial peptide is expected to be developed into a novel anti-infection drug and is used for preventing and treating various infections.

The invention relates to an N-terminal acetylation modified LMN-NKA polypeptide derivative or a pharmaceutically acceptable salt thereof and a preparation method of the N-terminal acetylation modified LMN-NKA polypeptide derivative, the chemical name of the LMN-NKA polypeptide derivative is N-acetyl-L-aspartic acid-L-lysine-L-phenylalanine-L-valine-glycine-N-methyl-L-leucine-L-n-leucine amide, and the structural formula of the N-terminal acetylation modified LMN-NKA polypeptide derivative is shown in the description. The structural general formula of the fluorescent probe is Ac-Asp-Lys-Phe-Val-Gly-N-Me-Leu-Nle-NH2, and the fluorescent probe has the structural formula shown in the description. According to the modification strategy, acetylation modification is only carried out on N-terminal free amino groups of a parent structure, natural amidation is reserved at a C terminal, other amino acid sequences and configurations are completely unchanged, the spatial conformation of a receptor binding site of the parent structure is not changed, meanwhile, the polarity of the polypeptide is reduced by closing the free amino groups, recognition and hydrolysis of aminopeptidase in a body are reduced, and the stability of the polypeptide is improved. The enzymolysis stability is remarkably improved, the modification process is simple, and no extra impurities are introduced. The LMN-NKA polypeptide derivative or the pharmaceutically acceptable salt thereof disclosed by the invention is particularly suitable for preparing a medicine for treating diseases related to an NK2 receptor.

Disclosed herein are leukocyte-targeting molecules, pharmaceutical compositions comprising leukocyte-targeting molecules and an optional pharmaceutical agent, and methods of using same. In some embodiments, a leukocyte-targeting molecule is a peptide having the formula: X1X2AAX3AX4X5X17AX6X7X8AX9X10A(P)nX11x12(X13)n, or a pharmaceutically acceptable salt thereof: wherein X1, X2, X11, and X12 are each, independently, lysine, arginine, or ornithine; X3, X4, X5, X6, X7, X8, X9, and X10 are each, independently, valine, leucine, isoleucine, or norleucine; X13 is tyrosine; X17 is praline or alanine; and n is 0 or 1.

The present application relates to a pharmaceutical composition for treatment or prevention of an inflammatory skin disease including atopic dermatitis and psoriasis, the pharmaceutical composition containing 6-diazo-5-oxo-L-norleucine or a pharmaceutically acceptable salt thereof.

The invention provides a 6-diazo-5-oxo-n-leucine prodrug and a preparation method and application thereof.According to the 6-diazo-5-oxo-n-leucine prodrug and a compound, a glutamine metabolism inhibitor JHU083 and an STING pathway agonist MSA-2 are connected through a cleavable amido bond, two action mechanisms are fused, the activity of the 6-diazo-5-oxo-n-leucine prodrug is improved, the activity of the 6-diazo-5-oxo-n-leucine prodrug is improved, and the activity of the 6-diazo-5-oxo-n-leucine prodrug is improved. On one hand, the metabolic advantage of tumor cells is limited, and the immunosuppressed tumor microenvironment is reversed; the STING pathway of dendritic cells is directly activated, immune factors such as type I interferon and tumor necrosis factor TNF-alpha are induced to release, and immune activation is synergistically enhanced; the dendritic cell function is improved, the antigen presentation capability is enhanced, the co-stimulatory molecule expression level of DC can be remarkably improved, the antigen presentation capability of the DC can be enhanced, the activation efficiency of T cells is improved, and the anti-tumor immune effect is enhanced; and the compound has good chemical stability and drug development potential, is suitable for further pharmacological research and preclinical development, and has good synthesizability and pharmaceutical properties.

The invention relates to an N-terminal palmitoylated / C-terminal ethylamine dual-modified LMN-NKA polypeptide derivative, a pharmaceutically acceptable salt thereof and a preparation method of the LMN-NKA polypeptide derivative. The chemical name of the LMN-NKA polypeptide derivative is N-palmitoyl-L-aspartic acid-L-lysine-L-phenylalanine-L-valine-glycine-N-methyl-L-leucine-L-n-leucine-ethylamine, and the structural formula of the LMN-NKA polypeptide derivative is Pal-Asp-Lys-Ph-Val-Gly-N-Me-Leu-Nle-NHCH2 CH3, and the structural formula of the LMN-NKA polypeptide derivative is shown in the description. According to the dual-modification strategy, the NK2 receptor binding capacity of the core active fragment of the neurokinin A can be specifically reserved, the enzymolysis stability, the fat solubility and the in-vivo metabolism stability are synergistically improved, the transmembrane efficiency is remarkably improved, and precise balance of water solubility and fat solubility is achieved. The polypeptide derivative and the salt thereof are especially suitable for preparing a long-acting therapeutic drug for NK2 receptor related chronic diseases.

The invention discloses a radix ranunculi ternati extract and a preparation method thereof. The radix ranunculi ternati extract is prepared from the following components: N-fructosyl isoleucine, N-fructosyl phenylalanine, N-linolenyl-4-aminobutyric acid, adenine, DL-arginine, 5-hydroxymethylfurfural, choline, cane sugar, adenosine, L-leucine, 1-palmitoyl-SN-glycerol-phosphorylcholine, N-linolenyl-4-aminobutyric acid, Boc-L-aspartic acid, sodium alginate, sodium alginate, sodium alginate and sodium alginate. Betaine and nicotinic acid. Compared with the prior art, the invention provides a brand new radix ranunculi ternati extract, the extract is extracted from a natural traditional Chinese medicine raw material radix ranunculi ternati, and the extract contains high-content active ingredients of amino acids, vitamins, nucleosides, saccharides and alkaloids, has multiple types of effective substances, and has a relatively high application value. And the preparation method is simple and worthy of further popularization.

The invention discloses an immunoaffinity separation method of hepatocyte-derived small extracellular vesicles in plasma and application of the immunoaffinity separation method, and relates to the technical field of biology. The separation method comprises the following steps: constructing a transgenic animal of which the hepatocyte specifically expresses the methionine-tRNA synthetase L274G mutant; the L-azido-n-leucine is administered into the transgenic animal, so that the transgenic animal expresses L-azido-n-leucine labeled protein; collecting and identifying L-azido-n-leucine labeled proteins in plasma-derived small extracellular vesicles, liver-derived small extracellular vesicles and liver tissues of the transgenic animal, carrying out cross analysis, and screening overlapped and highly expressed biomarkers; providing an antibody of the biomarker, and separating to obtain the hepatocyte-derived small extracellular vesicles in plasma through antigen-antibody specific binding. The effect of separating the hepatocyte-derived small extracellular vesicles by using the screened biomarker is remarkable, and a new thought and method are provided for disease diagnosis.

The application provides a biomarker combination specific to coronary sudden death and application and products thereof, and belongs to the technical field of forensic science.The biomarker combination comprises ascorbic acid, docosahexaenoic acid, carnitine, glutamine and norleucine.The biomarker combination is significantly changed in serum samples of individuals with coronary sudden death, and after ROC verification, shows good diagnostic performance, indicating that it has the potential to be applied to forensic identification of coronary sudden death.The potential application value of the non-targeted metabolomics strategy of the application in difficult and complex death cause identification provides a new idea for molecular diagnosis of death cause investigation.

The invention relates to an N-terminal lauroylation / C-terminal ethylamine dual-modified LMN-NKA polypeptide derivative, a pharmaceutically acceptable salt thereof and a preparation method of the LMN-NKA polypeptide derivative. The chemical name of the LMN-NKA polypeptide derivative is N-lauroyl-L-aspartic acid-L-lysine-L-phenylalanine-L-valine-glycine-N-methyl-L-leucine-L-n-leucine-ethylamine, and the structural formula of the LMN-NKA polypeptide derivative is Lau-Asp-Lys-Phe-Val-Gly-NMe-Leu-Nle-NHCH2 CH3, and the structural formula of the LMN-NKA polypeptide derivative is shown in the specification. According to the dual-modification strategy, the NK2 receptor binding capacity of the core active fragment of the neurokinin A can be specifically reserved, the enzymolysis stability, the fat solubility and the in-vivo metabolism stability are synergistically improved, the transmembrane efficiency is remarkably improved, and precise balance of water solubility and fat solubility is achieved. The polypeptide derivative and the salt thereof are especially suitable for preparing a long-acting therapeutic drug for NK2 receptor related chronic diseases.

The invention provides preparation of a novel 6-diazo-5-oxo-n-leucine derivative prodrug, the prodrug connects DON and artesunate through a breakable amido bond, selective targeting on tumor-related macrophages can be realized, the safety is higher, anti-tumor immune response can be effectively activated through polarization of M1 type macrophages, and the prodrug has a good application prospect in the field of tumor treatment. The phenomenon of drug resistance in treatment of cancers such as colorectal cancer is overcome. According to the preparation of the novel 6-diazo-5-oxo-n-leucine derivative prodrug provided by the invention, the prodrug has the beneficial effects of strong targeting property, remarkable anti-tumor activity, clear immune metabolism regulation mechanism, high safety, good development prospect and the like, and can be used for preparing drugs for treating cancers such as breast cancer, melanoma and colorectal cancer.

The invention relates to an N-terminal lauroylation modified LMN-NKA polypeptide derivative, a pharmaceutically acceptable salt of the N-terminal lauroylation modified LMN-NKA polypeptide derivative and a preparation method of the N-terminal lauroylation modified LMN-NKA polypeptide derivative, and the name of the LMN-NKA polypeptide derivative is N-lauroyl-L-aspartic acid, L-lysine, L-phenylalanine, L-valine, glycine, N-methyl-L-leucine and L-n-leucine. The structural formula of the compound is Lau-Asp-Lys-Phe-Val-Gly-N-Me-Leu-Nle, and the structural formula of the compound is shown in the specification. Through a single precise modification strategy of N-terminal lauroylation (C12 medium-long-chain fatty acid chain), the NK2 receptor binding capacity of a core active fragment of the neurokinin A can be specifically reserved, the enzymolysis stability, the fat solubility and the in-vivo metabolism stability are synergistically improved, the transmembrane efficiency is improved, the balance of water solubility and fat solubility is realized, and the application prospect is wide. Furthermore, the polypeptide derivative and the salt thereof can be used for preparing a long-acting treatment medicine for NK2 receptor related chronic diseases.

According to the 6-diazo-5-oxo-n-leucine derivative, the preparation method and the application, DON is released through a breakable amido bond, immunoregulation of sepsis-related macrophages can be achieved, the safety is high, immune response of sepsis mice can be effectively inhibited through polarization of M2 type macrophages, and the 6-diazo-5-oxo-n-leucine derivative has a good application prospect. Finally, the inflammation treatment of sepsis is realized. The derivative is a metabolic drug formed by connecting DON and leucine-PEG, the drug can be self-assembled into nano-particles, release DON to play an anti-inflammatory role and reduce systemic toxicity at inflammation parts with high esterase and amidase, and the derivative has good chemical stability and drug development potential, is suitable for further pharmacological research, and can be used for preparing a drug for treating inflammation. And the compound has good synthesizability and pharmaceutical properties.

Peptide compounds of formula (I): AA1-AA2-D-Ile-D-Tyr-AA3-D-Tyr-D-Ala-D-Tyr-D-Val-D-Ala-Gly-D-Ile-D-Leu-D-Lys-D-Arg-D-Trp-NH2 wherein, AA1 represents an amino acid selected from the group consisting of D-Tryptophan (D-Trp), D-1-naphthylalanine (D-1-Nal) and D-2-naphthylalanine (D-2-Nal); AA2 represents an amino acid selected from the group consisting of D-Leucine (D-Leu), D-Norleucine (D-Nle) and D-Phenylalanine (D-Phe); and AA3 represents an amino acid selected from the group consisting of D-Methionine (D- Met) and D-Norleucine (D-Nle), or a pharmaceutically acceptable salt thereof, which are useful in the treatment and / or prevention of cannabis use disorder.

The invention relates to an N-terminal palmitoylation modified LMN-NKA polypeptide derivative, a pharmaceutically acceptable salt of the N-terminal palmitoylation modified LMN-NKA polypeptide derivative and a preparation method of the N-terminal palmitoylation modified LMN-NKA polypeptide derivative, and the chemical name of the LMN-NKA polypeptide derivative is N-palmitoylation-L-aspartic acid-L-lysine-L-phenylalanine-L-valine-glycine-N-methyl-L-leucine-L-n-leucine. The structural formula of the compound is Pal-Asp-Lys-Phe-Val-Gly-N-Me-Leu-Nle, and the structural formula of the compound is shown in the specification. The NK2 receptor binding capacity of a core active fragment of neurokinin A (NKA) is specifically reserved through N-terminal single palmitoylation modification, meanwhile, the enzymolysis stability and fat solubility are remarkably improved, the transmembrane efficiency is improved compared with that of a natural LMN-NKA fragment, and the problem of water solubility caused by long-chain fatty acid modification is solved. The polypeptide derivative and the salt thereof are especially suitable for preparing a long-acting therapeutic drug for NK2 receptor related chronic diseases.