98453-81-7Relevant academic research and scientific papers
Protein-drug conjugate programmed by pH-reversible linker for tumor hypoxia relief and enhanced cancer combination therapy
Deng, Dashi,Dong, Ziliang,Feng, Liangzhu,Liu, Xiaowen,Liu, Zhuang,Wagner, Ernst,Xin, Xiaoqian,Yang, Zhijuan,Zhang, Xican
, (2020)
Combining functional proteins with small molecular drugs into one entity may endow distinct synergistic advantages. However, on account of completely different physicochemical properties of such payloads, co-delivery through systemic administration for therapeutic purpose is challenging. Herein, we designed the protein-drug conjugate HSAP-DC-CAT (human serum albumin/Pt (IV)-dibenzocyclooctyne/chlorin e6-catalase) by modification of CAT and cisplatin pro-drug loaded HSA with pH-sensitive azide linker 3-(azidomethyl)-4-methyl-2,5-furandione (AzMMMan) followed by click chemistry assembly with DC. The dynamic covalent bonds between linker and proteins, on the one hand, can bridge proteins and small molecular drugs in the intermediate state for systemic delivery in the harsh in vivo environment; on the other hand, it can trigger traceless cleavage and release of drugs and proteins with full bioactivity in acidic microenvironment of tumor. The multifunctional HSAP-DC-CAT provides efficient cytosolic transduction in vitro, excellent blood half-lives after systemic administration, and significant antitumor outcome via integrated cisplatin-based chemotherapy and Ce6-based photodynamic therapy enhanced by catalase-induced manipulation of tumor hypoxia microenvironment. This study describes a universal formulation strategy for protein and small molecular drug by a bifunctional linker through amide reaction and click chemistry, with traceless in vivo release of therapeutic units.
POLYMER OR POLYCONDENSATE BASED ON PEPTIDE, LINKER AND OPTIONALLY OTHER MONOMERS AND METHOD FOR PREPARING THE SAME
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Page/Page column 31-32, (2021/04/01)
The present invention concerns a method for producing polymers suitable as carrier-free delivery system of bioactive molecules, in particular bioactive peptides. The method comprises the polycondensation of one or more different monomers, including monomers comprising the peptides, monomers comprising a cross-linker and, optionally, monomers comprising an adjuvant. The invention also relates to the polymers obtained by the method, which are suitable as medicaments, such as vaccines. In a particular embodiment, the bioactive peptide is a neoantigen and the polymer is used as a cancer vaccine.
SUBSTITUTED AZOLE DIONE COMPOUNDS WITH ANTIVIRAL ACTIVITY
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Paragraph 00363; 00375, (2021/10/02)
Provided herein are methods of using substituted azole dione compounds for treatment of viral infections.
Acid-labile traceless click linker for protein transduction
Maier, Kevin,Wagner, Ernst
supporting information; experimental part, p. 10169 - 10173 (2012/08/08)
Intracellular delivery of active proteins presents an interesting approach in research and therapy. We created a protein transduction shuttle based on a new traceless click linker that combines the advantages of click reactions with implementation of reversible pH-sensitive bonds. The azidomethyl-methylmaleic anhydride (AzMMMan) linker was found compatible with different click chemistries, demonstrated in bioreversible protein modification with dyes, polyethylene glycol, or a transduction carrier. Linkages were stable at physiological pH but reversible at the mild acidic pH of endosomes or lysosomes. We show that pH-reversible attachment of a defined endosome-destabilizing three-arm oligo(ethane amino)amide carrier generates an effective shuttle for protein delivery. The cargo protein nlsEGFP, when coupled via the traceless AzMMMan linker, experiences efficient cellular uptake and endosomal escape into the cytosol, followed by import into the nucleus. In contrast, irreversible linkage to the same shuttle hampers nuclear delivery of nlsEGFP which after uptake remains trapped in the cytosol. Successful intracellular delivery of bioactive -galactosidase as a model enzyme was also demonstrated using the pH-controlled shuttle system.
Benzylic brominations with N-bromosuccinimide in (Trifluoromethyl)benzene
Suarez, Diana,Laval, Gilles,Tu, Shang-Min,Jiang, Dong,Robinson, Claire L.,Scott, Richard,Golding, Bernard T.
experimental part, p. 1807 - 1810 (2010/02/28)
A variety of benzylic brominations were performed by using N-bromosuccinimide in (trifluoromethyl)benzene with photochemical activation in the presence of 2,2′-azobisisobutyronitrile, 1,1′- azobis(cyclohexanecarbonitrile), or benzoyl peroxide as the radical initiator. This system provides clean, rapid, and high-yielding reactions with replacement of conventional solvents, such as tetrachloromethane, by less-toxic (trifluoromethyl)benzene. Georg Thieme Verlag Stuttgart.
Compounds with anti-cancer activity
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Page/Page column 72, (2008/12/08)
Novel substituted azole diones are provided that kill cells, suppress cell proliferation, suppress cell growth, abrogate the cell cycle G2 checkpoint and/or cause adaptation to G2 cell cycle arrest. Methods of making and using the invention compounds are provided. The invention provides substituted azole diones to treat cell proliferation disorders. The invention includes the use of substituted azole diones to selectively kill or suppress cancer cells without additional anti-cancer treatment. The invention includes the use of cell cycle G2-checkpoint-abrogating substituted azole diones to selectively sensitize cancer cells to DNA damaging reagents, treatments and/or other types of anti-cancer reagents.
A new strategy for the synthesis of furan-3,4-dicarboxylic acid
Deshpande, Anil M.,Natu, Arvind A.,Argade, Narshinha P.
, p. 1010 - 1012 (2007/10/03)
A facile route to furan-3,4-dicarboxylic acid is described. Dimethylmaleic anhydride (1) on NBS-bromination followed by aqueous KOH treatment gave bis(hydroxymethyl)maleic anhydride (3), which on intramolecular Mitsunobu ring closure followed by esterification and DDQ-oxidation furnished the desired esters of furan-3,4-dicarboxylic acid 7a/b.
