7 results about "Heparanase" patented technology

The invention relates to a drug testing method that enables the testing of inhibitor drugs against the heparanase enzyme, which plays a crucial role in the formation and proliferation of cancer cells, in a more cost-effective and faster manner. It involves the use of the DNS (3,5-Dinitrosalicylic acid) molecule.

The present invention is directed to hexasaccharides mimetics of heparins presenting remarkable heparanase inhibition activity. The compounds have formula (I), wherein R1 is selected from the group consisting of NH2, NHSO3Na, NHAc; R2 is selected from the group consisting of NH2, NHSO3Na, NHAc; R3 is selected from the group consisting of Bn, H; R4 is selected from the group consisting of Ac, H, SO3Na; R5 is CO2Na; R6 is selected from the group consisting of Me, Ethyl, Alkyl, alkyl azide, alkynyl, cholestanol aglycon; R7 is selected from the group consisting of CH2OH, COOH.

The present application provides a compound capable of simultaneously inhibiting heparanase and MMP activity, which is a compound shown in the following general formula: wherein A1 is a carbon atom or a nitrogen atom, A2 is a carbon atom; the bond A1-A2 is a single bond, a double bond, or is connected with a benzene ring or a cyclohexene ring; the five-membered ring can also be replaced by a six-membered ring. The compound has the functions of maintaining the integrity of epidermal structure, promoting the differentiation of keratinocytes, and regulating the function of skin barrier.

The application belongs to the technical field of bioengineering technology, and particularly relates to a heparanase and a preparation method and application thereof. The amino acid sequence of the heparanase (HPSE) is shown as SEQ ID NO. 2. The heparanase (WJS HPSE) provided in the application can specifically degrade HS glycan substrates, which are white jade snail polysaccharide (WJS PS) containing IdoA2S-GlcNAc disaccharide repeating units, heparin or HS. In addition, the heparanase (WJS HPSE) provided in the application has high thermal stability, has optimal enzyme activity at 57-67 DEG C and pH=4.0, significantly improves the stability and reuse efficiency in a catalytic process, and thus improves the application value of the HPSE.

The invention belongs to the technical field of immune cell therapy, and particularly relates to a heparanase-loaded CAR-T exosome and application thereof. According to the invention, the HPSE-loaded exosome is secreted by the engineered CAR-T cell, and the activity of the HPSE is limited in a tumor microenvironment (TME) by utilizing an anchoring mechanism, so that systematic off-target toxicity is avoided. The result of the embodiment shows that the exosome shows remarkable ECM degradation capacity, tumor killing efficiency and immune regulation function in in-vitro and in-vivo models, has the characteristics of simplicity in preparation, high safety and remarkable curative effect, and provides a new solution for solid tumor immunotherapy.

The invention discloses a peptidyl drug delivery system for overcoming tumor lysosome drug resistance isolation and a preparation method and application thereof. According to the peptidyl drug delivery system, functionalized polypeptide and heparin are subjected to multi-stage self-assembly to form nano-particles. The nanoparticles keep stable large particle size and electronegativity in the circulation stage; after administration in a tumor area, heparanase which is highly expressed in a tumor microenvironment is dissociated into small-particle-size electropositive particles with high tissue penetrating power; finally, under the synergistic activation of a lysosome acid environment and cathepsin B, the polypeptide is subjected to conformation transformation and self-assembly to form beta-folded nanofibers, and the integrity of a lysosome membrane is destroyed through a mechanical effect, so that an isolated drug is promoted to escape from the lysosome, and the lysosome-mediated drug resistance effect is effectively reversed. The invention is suitable for various treatment strategies including glioma radiotherapy and transcatheter arterial chemoembolism, and is used for solving the problem of lysosomal drug isolation in solid tumors.

The present invention is directed to synthetic hexasaccharide mimics of heparin having formula (I) wherein: R1 is selected from the group consisting of NH2, NHSO3 -, NHAc; R2 is selected from the group consisting of H, SO3 -, Bn, 2-Naphthylmethyl, preferably H; R3 is selected from the group consisting of H, Ac, SO3 -; R4 is CO2 -; R5 is Me, Et, C3-C30 linear or branched alkyl, optionally comprising one or more isolated or fused rings, PEG-OMe; R6 is selected from the group consisting of H, Ac, SO3 -; R is a C10-C30 linear or branched alkyl optionally comprising one or more isolated or fused rings. In another embodiment, the invention is directed to the use as a drug of hexasaccharides having the above formula, wherein R, R1, R2, R3, R4 and R6 have the above defined meaning, while R5 is selected from the group consisting of Me, Et, C3-C30 linear or branched alkyl, optionally comprising isolated or fused rings, PEG-OMe.