36results about "Kallidins/bradykinins" patented technology

Novel backbone cyclized peptide analogs are formed by means of bridging groups attached via the alpha nitrogens of amino acid derivatives to provide novel non-peptidic linkages. Novel building units disclosed are Nα(ω-functionalized) amino acids constructed to include a spacer and a terminal functional group. One or more of these Nα(ω-functionalized) amino acids are incorporated into a peptide sequence, preferably during solid phase peptide synthesis. The reactive terminal functional groups are protected by specific protecting groups that can be selectively removed to effect either backbone-to-backbone or backbone-to-side chain cyclizations. The invention is specifically exemplified by backbone cyclized bradykinin antagonists having biological activity. Further embodiments of the invention are somatostatin analogs having one or two ring structures involving backbone cyclization.

The present invention relates to certain biologically active peptides and conjugated peptides which can be used as therapeutics or prophylactics against diseases or conditions linked to B1 as the causative agent. In a preferred embodiment of the invention biologically active PEG-conjugated peptides are provided. In one aspect of the present invention, pharmacologically active PEG-conjugated peptides of the present invention are useful to treat inflammation or pain.

The present invention provides bradykinin peptide analogs, compositions, and methods of inhibiting thrombin-induced platelet and other cell activation. The bradykinin analogs comprise single or multiple peptide segments. The invention also provides a method for identifying compounds that selectively inhibit thrombin-induced platelet and other cell activation.

The present invention discloses compositions and methods for delivery of biomolecules into cells. Compositions comprise peptidomimetic macrocycles complexed or conjugated to biomolecules such as nucleic acids.

The invention provides a novel amino acid, neo-tryptophan, as well as polypeptides containing this novel amino acid such as neurotensin analogs. In addition, the invention provides neo-tryptophan derivatives, serotonin-like neo-tryptophan derivatives, and polypeptides containing such derivatives. The invention also provides methods for making neo-tryptophan, neo-tryptophan derivatives, serotonin-like neo-tryptophan derivatives, and compositions containing these compounds. Further, the invention provides methods for inducing a neurotensin response in a mammal as well as methods for treating a mammal having a serotonin recognition molecule.

The present invention discloses means and methods for the diagnosis, characterization, prognosis and treatment of cancer and specifically targeting cancer stem cells. The present invention provides an antibody that specifically binds to a non-hgand binding membrane proximal region of the extracellular domain of a human Notch receptor and inhibits tumor growth, and a method of treating cancer, wherein the method comprises administering the antibody for study subjects.

The invention provides methods for treating and / or preventing ocular disorders associated with increased intraocular pressure comprising administering a bradykinin B2 receptor agonist to a patient in need thereof.

The invention concerns a pseudopeptide compounds selected among the set constituted by:(i) the compounds of formula (I):in which:A1 represents a single bond, D-Arg or L-Lys;A2 represents L-Pro or trans-4-hydroxy-L-Pro (4Hyp);A3 represents L-Phe or L-thienylalanine (Thi);Y represents a hydrogen atom or a C1-C3 alkyl group;X represents a sulphur or oxygen atom; and,(ii) their additive salts. The invention also concerns the preparation and use of this compound and its additive salts in therapy.

The present invention relates to biologically active peptides and conjugated peptides useful as therapeutic or prophylactic agents against diseases or conditions associated with pathogenic factor B1. In a preferred embodiment of the present invention, biologically active PEG-conjugated peptides are provided. In one aspect of the invention, the pharmaceutically active PEG-conjugated peptides of the invention are useful in the treatment of inflammation or pain.

The invention provides a novel amino acid, neo-tryptophan, as well as polypeptides containing this novel amino acid such as neurotensin analogs. In addition, the invention provides neo-tryptophan derivatives, serotonin-like neo-tryptophan derivatives, and polypeptides containing such derivatives. The invention also provides methods for making neo-tryptophan, neo-tryptophan derivatives, serotonin-like neo-tryptophan derivatives, and compositions containing these compounds. Further, the invention provides methods for inducing a neurotensin response in a mammal as well as methods for treating a mammal having a serotonin recognition molecule.

The present invention relates to the modification of immunoglobulin molecules in which one or more cysteine ​​residues in the variable region which form intrachain disulfide bonds are replaced by amino acids which do not contain a sulfhydryl group and thus do not form disulfide bonds. The ability of these modified immunoglobulin molecules to induce an anti-idiotypic response is enhanced. The present invention further provides a method for treating or preventing tumors and / or infectious diseases using the modified immunoglobulin of the present invention.

The invention provides methods for treating and / or preventing ocular disorders associated with increased intraocular pressure comprising administering a bradykinin B2 receptor agonist to a patient in need thereof.

The present invention relates to bradykinin receptor modulators and pharmaceutical compositions thereof for use as a medicament for modulating collateral blood vessel growth of collateral arteries and / or other blood vessels of pre-existing arterial networks. The bradykinin receptor modulators of arteriogenesis are applicable in the treatment and / or prevention of disorders associated with defective blood flow or blood vessel malformation. A preferred aspect of the invention relates to bradykinin receptor agonists for use as a medicament for the prevention of cardiovascular ischemic disease in a patient at risk thereof. Further, the invention relates to a bradykinin receptor agonist for use in a method for treating a cardiovascular ischemic disease in a patient in need thereof, wherein said cardiovascular ischemic disease is a peripheral limb disease.

The present invention relates to the construction of a new class of Targeted Secretion Inhibitors (TSIs), which comprise a non-cytotoxic protease, translocation peptide and a targeting moiety peptide, wherein the targeting moiety peptide has a free N-terminal domain and a free C-terminal domain; to a single-chain fusion protein precursor thereof, and to a method of activating said single-chain fusion protein precursor.

The present invention relates to Notch-binding agents and Notch antagonists and methods of using the agents and / or antagonists for treating diseases such as cancer. The present invention provides antibodies that specifically bind to a non-ligand binding region of the extracellular domain of one or more human Notch receptor, such as Notch2 and / or Notch3, and inhibit tumor growth. The present invention further provides methods of treating cancer, the methods comprising administering a therapeutically effective amount of an antibody that specifically binds to a non-ligand binding region of the extracellular domain of a human Notch receptor protein and inhibits tumor growth.

In accordance with an embodiment of the present invention, a method is provided for defining the portion of one or more chemical compounds having binding affinity for a target receptor. One or more chemical compounds to be tested are identified and then one or more key component fragments of the compound(s) are identified (e.g., a compound that "generically" defines the surface conformation and surface charge density of the one or more chemical compounds is "designed") which may impart affinity for the target receptor. Analogs containing one or more of the key component fragments are then identified or synthesized, and the analogs are coupled to a carrier to construct an analog-carrier conjugate. The analogs contain one or more functional groups such as carboxyl, hydroxyl, keto, amino, nitro, or sulfhydryl to react with the carrier molecule. Next, the analog-carrier conjugate is utilized to generate a panel of monoclonal antibodies in vivo or in vitro, wherein the monoclonal antibodies are capable of defining the characteristics of the key component fragments. Next, the monoclonal antibodies are assayed to determine which are most specific for the key component fragments of the chemical compound(s) and which bind to the chemical compound(s). Competitive binding assays, or other assays are then preferably conducted to determine the ability of the monoclonal antibodies to discriminate between different chemical compounds.

This invention relates to the use of amine, amino acid or amino acid ester mobile phase modifiers in normal phase chromatography to improve the resolution and / or productivity of peptide and lipopeptide purification. This chromatographic method can be used for either on analytical or preparative scale purification.

The invention provides methods for treating and / or preventing ocular disorders associated with increased intraocular pressure comprising administering a bradykinin B2 receptor agonist to a patient in need thereof.

This invention relates to the use of amine, amino acid and amino acid ester mobile modifiers in normal phase chromatography to improve the resolution and or productivity of peptide and lipopeptide purification. This chromatographic method can be sued for either analytical or preparative scale purification.

The present invention relates to a new chemical process that provides novel carrier derivatives as excellent 1,2-aminothiol or 1,3-aminothiol specific reagents for use in For conjugation with unprotected targeting compounds (such as polypeptides, peptides or organic compounds) with or modified to have 1,2-aminothiol or 1,3-aminothiol groups. The invention also relates to methods of using the novel water-soluble polymer derivatives and conjugates thereof.

Bradykinin B1 receptor (B1R) targeting peptides and compounds are radiolabelled with radioisotopes that are suitable for imaging and / or radiotherapy. The radiolabelled peptides and compounds have utility in imaging tissues expressing or overexpressing B1R and / or treating diseases or conditions in which B1R is expressed or overexpressed, including cancer.

The present invention relates to bradykinin receptor modulators and pharmaceutical compositions thereof for use as a medicament for modulating collateral blood vessel growth of collateral arteries and / or other blood vessels of pre-existing arterial networks. The bradykinin receptor modulators of arteriogenesis are applicable in the treatment and / or prevention of disorders associated with defective blood flow or blood vessel malformation. A preferred aspect of the invention relates to bradykinin receptor agonists for use as a medicament for the prevention of cardiovascular ischemic disease in a patient at risk thereof. Further, the invention relates to a bradykinin receptor agonist for use in a method for treating a cardiovascular ischemic disease in a patient in need thereof, wherein said cardiovascular ischemic disease is a peripheral limb disease.

A synthetic peptide brap can be used in preparing an anti-inflammatory drug for COVID-19. The amino acid sequence of the synthetic peptide brap is as shown in SEQ ID No. 1. The synthetic peptide brap has significant target-docking and inhibiting effects on G-protein-coupled bradykinin B1 and B2 receptors; the intranasal administration of brap has local effects on allergic nasal inflammation, and has systemic pharmacodynamic effect on pulmonary leakage, lung injury and LPS-induced cytokine storm. The intravenous injection of brap has an obvious inhibiting effect on the excessive inflammation, oxidative stress response and serious lung injury emerging in LPS-induced mice; and has an obvious inhibiting effect on the excessive release of proinflammatory factors IL-6 and TNF-α, overexpression of IL-6 mRNA, and massive generation of reactive oxygen species (ROS) in the LPS-induced inflammatory factor storm.

The invention belongs to a field of pharmacy, relates to a field of protein polypeptide biological technology, and more specifically relates to a polypeptide which specifically binds to a bradykinin acceptor. The invention employs a polypeptide sequence overturn principle, and the bradykinin is used as a template for designing a polypeptide, whose amino acid sequences are as follows: RI-BK is RFPSFGPPR; RI-KD is PFPSFGPPRK; RRI-L-BK is RFPSFGPPRL. Experiments show that: the polypeptide has a high affinity for the bradykinin acceptor, can selectively open blood-brain tumor barriers, substantially improves accumulation of the medicament in the brain tumor and prolonging the lifetime of a glioma in-situ model nude mouse. The polypeptide of the present invention can be used for preparing adjuvant drugs of chemotherapeutics, and is used for preparing a combination drug for treating brain tumor together with a polymer micelle administration system which envelops the tumor medicament.

The present invention relates to composition of matter involving bradykinin B1 receptor antagonist peptides conjugated to a multivalent vehicle, including peptides conjugated to multivalent PEG. These compositions can be used as therapeutics or prophylactics against diseases or conditions, such as inflammation or pain, linked to the bradykinin B1 receptor.

The invention discloses bullfrog slow-excitation peptide, coded nucleic acid thereof and application. The bullfrog slow-excitation peptide is composed of nine parts of amino acid, the molecular weight is 1043.2 daltons, the isoelectric point is 9.50, and the amino acid sequence is SEQ ID NO. 4: Arg Pro Pro Gly Cys Asn Pro Phe Arg. The sequence of the encoded gene of the bullfrog slow-excitation peptide is the 156-183th nucleotide of the sequence shown by the SEQ ID NO.1. The bullfrog slow-excitation peptide is composed of sixteen parts of amino acid, the molecular weight is 1759.0 daltons, the isoelectric point is 10.35, and the sequence of the amino acid is SEQ ID NO. 6: Arg Pro Pro Gly Cys Asn Pro Phe Arg Ile Ala Pro Ala Ser Tyr Leu. According to the bullfrog slow-excitation peptide, the coded nucleic acid thereof and the application, the amino acid structure of the bullfrog slow-excitation peptide is deduced through the coded gene of the bullfrog slow-excitation peptide, and the synthetic bullfrog slow-excitation peptide RR9 and RL16 have very strong activity for promoting contraction of in-vitro ileum muscle of rats. The bullfrog slow-excitation peptide has the advantages of being simple in structure and convenient to synthesize artificially, so that the bullfrog slow-excitation peptide can serve as cardio-cerebral-vascular drug and application of medicine for promoting intestinal contraction.

The present invention provides a process for the manufacture of peptidomimetic drug icatibant with high yield and purity by fragment condensation on the solid phase. In particular, it describes a convergent synthesis by condensation of a protected C-terminal fragment bound to a solid support and a protected N-terminal fragment, followed by cleavage from the support and resulting in a crude peptide of high purity, which is further purified to obtain pure icatibant in high yield. The invention further provides intermediates useful in the manufacturing process.