6 results about "Enediyne" patented technology

The invention provides a conjugated enyne compound, a preparation method and application thereof, a pharmaceutical composition and application thereof, and relates to the technical field of biological medicines. The conjugated enyne compound provided by the invention has the structural characteristics that the positions 5 and 6 and the positions 9 and 10 are acetylenic bonds, the C-12 position is substituted with acetylcysteine residues, the conjugated enyne compound is a derivative of endiyne biosynthesis precursor 1, 3, 5, 7, 9, 11, 13-pentadecene, the biosynthesis route of endiyne relates to an actinomycete mercaptan (MSH) detoxification mechanism, and the conjugated enyne compound can be used for preparing an actinomycete thiol compound. It is revealed that an MSH-dependent enzymatic detoxification mechanism participates in biosynthesis of endiyne, plays an important role in antibiotic resistance and environmental adaptation of endiyne strains, and also brings brand new reference and thinking for analysis of biosynthesis pathways of endiyne. In addition, the conjugated enyne compound provided by the invention has good anti-tumor activity.

The invention relates to compounds of general structure (1): Q-(L1)n-(L2)o-(L3)p-(L4)q-D (1), wherein Q is a click probe; D is a cytotoxin containing an enediyne moiety; L1, L2, L3 and L4 are each individually linkers that together link Q to D; n, o, p and q are each individually 0 or 1, provided that n+o+p+q=1, 2, 3 or 4, wherein D comprises a functional moiety (21):wherein R12=C1-3-alkyl, the wavy line indicates the connection to the remainder of the cytotoxin, and wherein D is conjugated to (L4)q by replacing the amine H atom, and to conjugates obtainable by reacting the compound according to the invention with a protein comprising a click probe F capable of reacting with click probe Q in a click reaction. The invention further relates to a bioconjugate according to general structure (2): Pr-[(L6)-Z-(L1)n-(L2)o-(L3)p-(L4)q-D]xx (2), wherein Z is a connecting group that is formed in a click reaction, L6 is a linker that links Z to Pr and Pr is a (glyco)protein.

The present invention concerns antibody-conjugates which are especially suitable for the targeting of PTK7-expressing cells, in particular tumour cells. The antibody-conjugates according to the invention have structure (1):AB-[(L6)b-{Z-L-D}x]y  1Herein, AB is an antibody capable of targeting PTK7-expressing tumours; L is a linker that links Z to D; Z is a connecting group; L6 is -GlcNAc(Fuc)w-(G)j-S-(L7)w′-, wherein G is a monosaccharide, j is an integer in the range of 0-10, S is a sugar or a sugar derivative, GlcNAc is N-acetylglucosamine and Fuc is fucose, w is 0 or 1, w′ is 0, 1 or 2 and L7 is —N(H)C(O)CH2—, —N(H)C(O)CF2— or —CH2—; D is selected from the group consisting of anthracyclines, camptothecins, tubulysins, enediynes, amanitins, duocarmycins, maytansinoids, auristatins, eribulins, BCL-XL inhibitors, hemiasterlins, KSP inhibitors, TLR agonists, indolinobenzodiazepine dimers or pyrrolobenzodiazepine dimers (PBDs), and analogues or prodrugs thereof; b is 0 or 1; x is 1 or 2; and y is 1, 2, 3 or 4. The invention further concerns a method for preparing the antibody-conjugates of structure (1) and application of the antibody-conjugates of structure (1).

The present invention concerns antibody-conjugate having general structure (2):AB-[(L6)-{Z—(L1)n—(L2)o—(L3)p—(L4)q-D}xx]yy   (2)wherein AB is an antibody capable of targeting Trop-2-expressing tumours and D is selected from the group consisting of taxanes, anthracyclines, camptothecins, epothilones, mytomycins, combretastatins, vinca alkaloids, maytansinoids, enediynes such as calicheamicins, duocarmycins, tubulysins, amatoxins, bleomycins, dolastatins and auristatins, pyrrolobenzodiazepine dimers, indolinobenzodiazepine dimers, radioisotopes, therapeutic proteins and peptides (or fragments thereof), kinase inhibitors, MEK inhibitors, KSP inhibitors, and analogues or prodrugs thereof. These antibody-conjugates exhibit an improved therapeutic index. The invention further concerns a process for preparing the antibody-conjugate according to the invention, a method for targeting Trop-2-expressing cells, medical uses of the antibody-conjugates according to the invention.

The invention belongs to the field of organic chemical synthesis, and relates to a method for synthesizing ester-substituted polycyclic N-heteroaromatic compounds. The preparation method comprises the following steps: mixing an endiyne compound 1 with a photocatalyst, alkali and a first solvent to obtain a first mixed solution; mixing an alkyl acyl chloride compound 2 with a second solvent to obtain a second mixed solution; and respectively and simultaneously pumping the first mixed solution and the second mixed solution into a microchannel reactor of a microchannel reaction device through an injection pump, and carrying out a photoreaction to obtain the ester-substituted polycyclic N-heteroaromatic compound 3. The alkene diyne compound and the alkyl acyl chloride compound used in the invention are cheap and easily available. According to the synthesis method provided by the invention, ester-substituted polycyclic N-heteroaromatic hydrocarbon can be synthesized from an enediyne compound under a mild condition through a free radical mediated mechanism, and the synthesis method is simple to operate and environment-friendly.

The present invention concerns antibody-conjugates which are especially suitable for the targeting of PTK7-expressing cells, in particular tumour cells. The antibody-conjugates according to the invention have structure (1):Herein, AB is an antibody capable of targeting PTK7-expressing tumours; L is a linker that links Z to D; Z is a connecting group; L6 is -GlcNAc(Fuc)w-(G)j-S-(L7)w′-, wherein G is a monosaccharide, j is an integer in the range of 0-10, S is a sugar or a sugar derivative, GlcNAc is N-acetylglucosamine and Fuc is fucose, w is 0 or 1, w′ is 0, 1 or 2 and L7 is —N(H)C(O)CH2—, —N(H)C(O)CF2— or —CH2—; D is selected from the group consisting of anthracyclines, camptothecins, tubulysins, enediynes, amanitins, duocarmycins, maytansinoids, auristatins, eribulins, BCL-XL inhibitors, hemiasterlins, KSP inhibitors, TLR agonists, indolinobenzodiazepine dimers or pyrrolobenzodiazepine dimers (PBDs), and analogues or prodrugs thereof; b is 0 or 1; x is 1 or 2; and y is 1, 2, 3 or 4. The invention further concerns a method for preparing the antibody-conjugates of structure (1) and application of the antibody-conjugates of structure (1).