- Chitosan-Based Peptidopolysaccharides as Cationic Antimicrobial Agents and Antibacterial Coatings
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The rapid spread of multidrug-resistant bacteria has called for effective antimicrobial agents which work on a more direct mechanism of killing. Cationic peptidopolysaccharides are developed in the present work to mimic the peptidoglycan structure of bacteria and to enhance the membrane-compromising bactericidal efficacy. Antimicrobial CysHHC10 peptide was grafted to the C-2 (amino) or C-6 (hydroxyl) position of chitosan backbone via thiol-maleimide "click" conjugation, utilizing the maleimidohexanoic linkers. The peptidopolysaccharide with primary amino backbone intact (CSOHHC) exhibited higher bactericidal activity toward Gram-positive and Gram-negative bacteria, in comparison to that with amino backbone grafted with the peptide (CSNHHC). Both peptidopolysaccharides also exhibited lower hemolytic activity and cytotoxicity than free CysHHC10 peptide due to the moderation effect contributed by the chitosan backbone. For targeting the Gram-positive bacteria in particular, the CSOHHC expressed 4- and 2-fold increases in hemo- and cytoselectivity, respectively, as compared to the CysHHC10 peptide. In an extended application, peptidopolysaccharide antibacterial coatings were formed via layer-by-layer assembly with tannic acid. The peptidopolysaccharide coatings readily killed the adhered bacteria upon contact while being cytocompatible by maintaining more than 60% viability for the adhered fibroblasts. Therefore, the peptidoglycan-mimetic peptidopolysaccharides are potential candidates for anti-infective drugs in biomedical applications.
- Pranantyo, Dicky,Xu, Li Qun,Kang, En-Tang,Chan-Park, Mary B.
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- Clustered nanobody-drug conjugates for targeted cancer therapy
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A clustered Nb-drug conjugate (cNDC?PEG) was designed using anti-EGFR Nb to specifically deliver Pt(iv) prodrugs to tumors. cNDC?PEG efficiently targets EGFR positive tumor cells, and the clustered cNDC?PEG is more efficient in inhibiting tumor growth in vivo than the monomeric NDC. This work provides a novel strategy for the construction of a multi-valent NDC using dendrimers. This journal is
- Huang, Hai,Liu, Manman,Liu, Yangzhong,Sheng, Yaping,Wu, Tiantian,Xiao, Haihua
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- Reversible crosslinking of lignin via the furan-maleimide Diels-Alder reaction
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Two distinct functionalization schemes for Kraft lignin (KL) were developed to selectively incorporate furan and/or maleimide motifs as chain ends. The incorporation of furan functionalities was carried out by the selective and quantitative reaction of the lignin's phenolic OH groups with furfuryl glycidyl ether (FGE). Maleimide groups were introduced by esterifying the lignin's aliphatic and phenolic OH groups with 6 maleimidohexanoic acid (6-MHA), offering a high loading despite a somewhat incomplete conversion. Furan- and maleimide-functionalized lignins were subsequently combined to generate crosslinking via the Diels-Alder (DA) [4 + 2] cycloaddition reaction. The formation of the DA adduct was confirmed by 1H NMR. Under appropriate conditions, the formation of a gel was apparent, which turned back into the liquid state after performing the corresponding retro-DA reaction upon heating to 120 °C. This study reveals the significant versatility and potential of the developed strategy for the utilization of lignin-based recyclable networks.
- Duval, Antoine,Lange, Heiko,Lawoko, Martin,Crestini, Claudia
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- Honokiol Prodrug Nanoparticles Based on in Situ Albumin Binding for Long Circulation and High Tumor Uptake
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Honokiol (HK) has antiproliferation effects against numerous cancer cells, but its low solubility and bioavailability impede its application. In this study, a prodrug of HK (HP) featuring a maleimide group was synthesized and then mixed with tocopherol polyethylene glycol succinate to prepare prodrug nanoparticles (HP-NPs). In vitro albumin binding experiments showed that HP rapidly reacted with the cysteine thiols of albumin to form a covalent conjugate that released HK slowly in the LLC tumor cell line. In vitro cell apoptosis and uptake assays showed that the cellular uptake of the HK increased into the LLC cells as the albumin concentration increased. Strikingly, in vivo pharmacokinetics and pharmacodynamics measurements demonstrated that the HP-NPs significantly prolonged the circulation and increased tumor accumulation. Taken together, our study demonstrated, both in vitro and in vivo, that the albumin-based HP-NPs delivery system holds significant potential toward the treatment of lung cancer in clinical studies.
- Chen, Lixue,Chen, Yali,Ding, Yanfang,Gao, Meng,Li, Hang,Li, Lei,Li, Shengnan,Ma, Xiaodong,Qi, Yan,Wang, Changyuan,Xu, Ruping,Xu, Youwei,Zhang, Sitong
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supporting information
p. 1589 - 1595
(2021/10/12)
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- ANTIBODY DRUG CONJUGATES OF KINESIN SPINDEL PROTEIN (KSP) INHIBITORS WITH ANTIB7H3-ANTIBODIES
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The present application relates to novel binder drug conjugates (ADCs), to active metabolites of these ADCs, to processes for preparing these ADCs, to the use of these ADCs for the treatment and/or prophylaxis of diseases and to the use of these ADCs for preparing medicaments for treatment and/or prophylaxis of diseases, in particular hyperproliferative and/or angiogenic disorders such as, for example, cancer diseases. Such treatments can be effected as monotherapy or else in combination with other medicaments or further therapeutic measures.
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Paragraph 0962
(2020/05/29)
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- Photopolymerization of maleimide perfluoropolyalkylethers without a photoinitiator
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Perfluoropolyalkylethers derived from hexafluoropropylene oxide were functionalized with maleimide groups. Irradiated by UV-light, the new maleimide macromonomers demonstrated very fast polymerization kinetics with a curing time as fast as 8 s. The effect on photopolymerization of different features such as the molecular weight of the fluorinated chain and the chain length of the hydrogenated spacer were studied, as well as the influence of the type of photoinitiator and the presence of air. Thermal and surface properties of the UV-cured polymers were examined and were typical to fluoropolymers in view of water–oil repellent coatings.
- Bonneaud, Céline,Burgess, Julia M.,Bongiovanni, Roberta,Joly-Duhamel, Christine,Friesen, Chadron M.
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p. 699 - 707
(2019/01/04)
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- DELIVERY SYSTEMS FOR CONTROLLED DRUG RELEASE
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The present invention provides a compound having the structure of Formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, or isomer thereof, for the controlled delivery and release of Agent.
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Paragraph 0405; 0407
(2019/01/15)
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- MAYTANSINOID-BASED DRUG DELIVERY SYSTEMS
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The present subject matter provides for albumin-binding prodrugs, maytansinoid-based compounds, and uses thereof.
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Paragraph 00130; 00133
(2019/06/17)
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- ALBUMIN-BINDING PRODRUGS OF AURISTATIN E DERIVATIVES
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The present disclosure provides for albumin-binding prodrugs of auristatin E derivatives and uses thereof.
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Paragraph 00165
(2019/06/17)
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- Synthesis and anti-cancer evaluation of folic acid-peptide- paclitaxel conjugates for addressing drug resistance
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The drug resistance and the poor water solubility are major limitations of paclitaxel (PTX) of based chemotherapy. To conquer the two problems, targeting folate (FA) receptor PTX-lytic peptides conjugates were synthesized and evaluated. Compared with PTX, FA-P3-PTX and FA-P7-PTX displayed significantly enhanced cell toxicity in many cancer cells, particularly drug resistant cancer cells MCF-7/PTX. FA-P7-PTX possessed stronger effect on cell toxicity (IC50 = 2.92 ± 0.2 μM), membrane disrupting activity and pro-apoptosis in MCF-7/PTX cells than FA-P3-PTX. Further investigation displayed that the anti-cancer mechanisms of FA-P3-PTX and FA-P7-PTX might be a mitochondrial impairment and caspase-3-dependent apoptotic cell death. Furthermore, the in vivo antitumor efficacy study confirmed that FA-P7-PTX performed more stronger potency in inhibition of tumors growth than PTX. The study demonstrated that conjugate FA-P7-PTX with superior properties for antineoplastic activity, which makes it a promising potential candidate for drug-resistant cancer therapy.
- Dai, Yuxuan,Cai, Xingguang,Bi, Xinzhou,Liu, Chunxia,Yue, Na,Zhu, Ying,Zhou, Jiaqi,Fu, Mian,Huang, Wenlong,Qian, Hai
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p. 104 - 115
(2019/03/26)
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- Preparation method of heterobifunctional protein cross-linking agent having hydrazide structure
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The invention relates to the technical field of preparation of compounds, in particular to a preparation method of a heterobifunctional protein cross-linking agent having a hydrazide structure. The method comprises the following steps: enabling maleimide alkyl acid, i.e., a compound A to be subjected to a heating reaction under the action of a solvent and sulfoxide chloride so as to enable a carboxyl group in the structure of the compound A to be converted into acyl chloride; mixing obtained maleimide alkyl acyl chloride with a solvent and various types of compounds B, and performing an acylation reaction under the action of organic or inorganic alkali so as to generate a compound C; and removing a protecting group at the hydrazine end of the compound C under the action of a solvent and acid or alkali so as to obtain maleimide alkyl hydrazide having the hydrazide structure. According to the method involved in the invention, the cheap and readily available maleimide alkyl acid, as a starting raw material, is prepared into the maleimide alkyl hydrazide by three steps of reactions; the yield of a synthetic route is higher; a product is suitable for the research and development and production of an antibody-drug conjugate; and a synthesis method is simple and convenient to operate, safe and controllable, and suitable for industrial production.
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Paragraph 0014
(2019/04/10)
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- ANTIBODY DRUG CONJUGATES (ADCS) AND ANTIBODY PRODRUG CONJUGATES (APDCS) WITH ENZYMATICALLY CLEAVABLE GROUPS
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The present invention relates to novel binder-prodrug conjugates (APDCs) where binders are conjugated with inactive precursor compounds of kinesin spindle protein inhibitors, and to antibody-drug conjugates ADCs and to processes for producing these APDCs and ADCs.
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- Active custom white [...] drug delivery carrier and its use in pharmacy (by machine translation)
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The invention belongs to the pharmaceutical preparation of the new materials and new formulation field, relates to in order to endogenous white protein as the target of the drug delivery system design and application. The use of active custom white [...] carrier material, in order to maleic imide as a target head, polyethylene glycol as the flexibility of the [...] connected to flay, hydrophobic material (such as PLGA, such as stearic acid) as the anchoring part. This carrier material preparation of nano delivery formulation can be entrapped a plurality of anti-tumor drug, and can through its surface maleimide active combined [...], tumor blood vessel and tumor cells with high expression of albumin receptor (SPARC, gp60) interaction, overcome the various biological transfer barrier, effectively improve the nano particles accumulating in tumor site of, tumor cell uptake and anti-tumor activity. The nano-delivery formulation stability is good, high safety, target best, can be used for intravenous injection, large market application prospect. (by machine translation)
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Paragraph 0018; 0021; 0056-
(2018/08/03)
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- COMPOSITION FOR THE TREATMENT OF IGF-1R EXPRESSING CANCER
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The present invention relates to a method for the treatment of IGF-IR expressing cancers as well as to a compositions and a kit for said traitment. From one aspect, the invention reates to the combined use of a first antibody for the determination of the IGF-IR status of a cancer and a second antibody used as an ADC for the treatment of said cancer.
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Page/Page column 179
(2017/05/17)
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- DRUG-LINKER CONJUGATE PHARMACEUTICAL COMPOSITIONS
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Compositions are disclosed having a cytotoxic and/or vascular disrupting agent (VDA) payload attached to a linker. The linker can be a cathepsin B protease cleavable linker or a non-cleavable linker that may degrade intracellularly. Methods for making and using the compositions are also provided. The compositions can be provided to a patient in need thereof with the composition coming into contact with a cancer cell to activate or release the cytotoxic and/or vascular disrupting agent payload.
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Paragraph 000175
(2017/05/02)
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- CONJUGATE OF MONOMETHYL AURISTATIN F AND TRASTUZUMAB AND ITS USE FOR THE TREATMENT OF CANCER
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The present invention relates to an antibody-drug-conjugate or pharmaceutical composition comprising the same. From one aspect, the invention relates to an antibody-drug-conjugate (ADC) comprising an antibody consisting of the Trastuzumab or a biosimilar thereof, said antibody being conjugated to at least one drug consisting of a monomethyl auristatin F derivative. The invention also comprises method of treatment of cancer comprising administering to the subject an effective amount of said antibody-drug-conjugate or composition comprising the same.
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Paragraph 0531; 0532
(2017/05/15)
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- LIGAND-CYTOTOXICITY DRUG CONJUGATE, PREPARING METHOD THEREFOR, AND APPLICATION THEREOF
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Provide are a ligand-cytotoxicity drug conjugate with a general formula of PC-L-Dr, a preparing method thereof, and applications of the ligand-cytotoxicity drug conjugate and pharmaceutical compositions comprising the same in preparing drugs for treating cancers by means of receptor regulation.
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Paragraph 0098; 0133; 0134
(2017/12/31)
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- CONJUGATE OF MONOMETHYL AURISTATIN F AND TRASTUZUMAB AND ITS USE FOR THE TREATMENT OF CANCER
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The present invention relates to an antibody-drug-conjugate. From one aspect, the invention relates to an antibody-drug-conjugate comprising an antibody consisting of the Trastuzumab, said antibody being conjugated to at least one drug consisting of a monomethyl auristatin F derivative. The invention also comprises method of treatment and the use of said antibody-drug-conjugate for the treatment of cancer.
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Page/Page column 109
(2016/11/17)
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- Synthesis of Lactones via C-H Functionalization of Nonactivated C(sp3)-H Bonds
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An electron-deficient amide is utilized as a directing group to functionalize nonactivated C(sp3)-H bonds through radical 1,5-hydrogen abstraction. The γ-bromoamides formed are subsequently converted to γ-lactones under mild conditions. The method described is not limited to tertiary and secondary positions but also allows functionalization of primary nonactivated sp3-hybridized positions in a one-pot sequence. In addition, the broad functional group tolerance renders this method suitable for the late-stage introduction of γ-lactones into complex carbon frameworks.
- Richers, Johannes,Heilmann, Michael,Drees, Markus,Tiefenbacher, Konrad
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supporting information
p. 6472 - 6475
(2016/12/23)
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- IGF-1R ANTIBODY-DRUG-CONJUGATE AND ITS USE FOR THE TREATMENT OF CANCER
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The present invention relates to an antibody-drug-conjugate capable of binding IGF-1R. From one aspect, the invention relates to an antibody-drug-conjugate comprising an antibody capable of binding to IGF-1R, said antibody being conjugated to at least one drug selected from derivatives of dolastatin 10 and auristatins. The invention also comprises method of treatment and the use of said antibody-drug- conjugate for the treatment of cancer.
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Page/Page column 179
(2015/11/16)
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- 1-(CHLOROMETHYL)-2,3-DIHYDRO-1H-BENZO[E]INDOLE DIMER ANTIBODY-DRUG CONJUGATE COMPOUNDS, AND METHODS OF USE AND TREATMENT
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The invention provides antibody-drug conjugates comprising an antibody conjugated to a 1-(chloromethyl)-2,3-dihydro-1H-benzo[e]indole (CBI) dimer drug moiety via a linker, and methods of using the antibody-drug conjugates.
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Page/Page column 113
(2015/02/25)
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- ANTIBODY-DRUG-CONJUGATE AND ITS USE FOR THE TREATMENT OF CANCER
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The present invention relates to an antibody-drug-conjugate. From one aspect, the invention relates to an antibody-drug-conjugate comprising an antibody capable of binding to a Target, said antibody being conjugated to at least one drug selected from derivatives of dolastatin 10 and auristatins. The invention also comprises method of treatment and the use of said antibody-drug-conjugate for the treatment of cancer.
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Page/Page column 248
(2015/11/10)
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- CYTOTOXIC PEPTIDES AND ANTIBODY DRUG CONJUGATES THEREOF
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The present invention is directed to cytotoxic pentapeptides, to antibody drug conjugates thereof, and to methods for using the same to treat cancer.
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Page/Page column 224
(2013/06/05)
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- CYTOTOXIC PEPTIDES AND ANTIBODY DRUG CONJUGATES THEREOF
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The present invention is directed to cytotoxic pentapeptides, to antibody drug conjugates thereof, and to methods for using the same to treat cancer.
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Page/Page column
(2013/06/04)
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- Trans,trans-2,4-Hexadiene incorporation on enzymes for site-specific immobilization and fluorescent labeling
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Lipase B from Candida antarctica (CAL-B) has been site-directedly modified by the introduction of a trans,trans-hexadiene moiety onto lipase molecules, identified by MALDI-TOF. This modification on CAL-B permitted its immobilization on Q-Sepharose supports in excellent yields (>95%) when native lipase was not immobilized at pH 7 and 25 °C. After the entire modification procedure, the catalytic activity of the protein on the solid support was surprisingly increased 2-fold. A tailor-made maleimide-fluorophore derivative was specifically covalently linked to the protein in high yield via a selective Diels-Alder reaction in aqueous media. Furthermore, the NBD-labeled-CAL-B was also immobilized on the ionic support, retaining around 80% of the specific activity. The preparation of this labeled-CAL-B was also possible by a Diels-Alder reaction on solid phase in excellent yields.
- Filice, Marco,Romero, Oscar,Guisan, Jose M.,Palomo, Jose M.
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experimental part
p. 5535 - 5540
(2011/08/07)
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- RECEPTOR AND ANTIGEN TARGETED PRODRUG
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The present invention relates to a prodrug which comprises at least one pharmaceutically and/or diagnostically active compound bound by a cleavable linker, a receptor and/or antigen targeting moiety and a protein-binding moiety which is capable of binding to a carrier molecule.
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Page/Page column 22
(2008/12/08)
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- BIODEGRADABLE OCULAR IMPLANTS AND METHODS FOR TREATING OCULAR CONDITIONS
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Biodegradable ocular implants are described. The ocular implants include a bioactive agent that can be released within the eye to treat an ocular condition or indication. The implants can be used for the administration of a bioactive agent over prolonged periods of time. In some aspects the implants are formed of a matrix of natural biodegradable polysaccharides.
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Page/Page column 46-47
(2008/12/05)
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- Tissue graft materials containing biocompatible agent and methods of making and using same
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The invention provides implantable tissue graft materials composed of a collagenous tissue scaffold and a biocompatible agent bonded to the tissue scaffold via an activated photoreactive group. The invention further provides methods including steps of obtaining a tissue graft material comprising a collagenous tissue scaffold; contacting the collagenous tissue scaffold with a biocompatible agent composition that includes biocompatible agent and one or more photoreactive groups; and treating the collagenous tissue scaffold and biocompatible agent composition to activate the photoreactive groups and bond the biocompatible agent to the tissue scaffold via one or more activated photoreactive groups. Implantable prostheses formed of the tissue graft material are also contemplated.
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Page/Page column 16
(2010/11/30)
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- MONOMETHYLVALINE COMPOUNDS HAVING PHENYLALANINE SIDE-CHAIN MODIFICATIONS AT THE C-TERMINUS
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Auristatin peptide analogs of MeVal-Val-Dil-Dap-Phe (MMAF) are provided having C-terminal phenylalanine residue side chain replacements or modifications which are provided alone or attached to ligands through various linkers. The rlated conjugates can target specific cell types to provide therapeutic benefit.
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Page/Page column 140; 223
(2008/06/13)
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- MONOMETHYLVALINE COMPOUNDS HAVING PHENYLALANINE CARBOXY MODIFICATIONS AT THE C-TERMINUS
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Auristatin peptide analogs of MeVal-Val-Dil-Dap-Phe (MMAF) having a carboxylic acid equivalent at the C-terminal phenylalanine were prepared and attached to ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo.
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Page/Page column 111; 143; 144; 152; 167
(2008/06/13)
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