28170-07-2Relevant articles and documents
Platform to Discover Protease-Activated Antibiotics and Application to Siderophore-Antibiotic Conjugates
Boyce, Jonathan H.,Dang, Bobo,Ary, Beatrice,Edmondson, Quinn,Craik, Charles S.,Degrado, William F.,Seiple, Ian B.
, p. 21310 - 21321 (2020)
Here we present a platform for discovery of protease-activated prodrugs and apply it to antibiotics that target Gram-negative bacteria. Because cleavable linkers for prodrugs had not been developed for bacterial proteases, we used substrate phage to discover substrates for proteases found in the bacterial periplasm. Rather than focusing on a single protease, we used a periplasmic extract of E. coli to find sequences with the greatest susceptibility to the endogenous mixture of periplasmic proteases. Using a fluorescence assay, candidate sequences were evaluated to identify substrates that release native amine-containing payloads. We next designed conjugates consisting of (1) an N-terminal siderophore to facilitate uptake, (2) a protease-cleavable linker, and (3) an amine-containing antibiotic. Using this strategy, we converted daptomycin - which by itself is active only against Gram-positive bacteria - into an antibiotic capable of targeting Gram-negative Acinetobacter species. We similarly demonstrated siderophore-facilitated delivery of oxazolidinone and macrolide antibiotics into a number of Gram-negative species. These results illustrate this platform's utility for development of protease-activated prodrugs, including Trojan horse antibiotics.
Cationic lipid molecule, and application thereof in nucleic acid delivery
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Paragraph 0162-0165, (2019/10/08)
The present invention discloses a cationic lipid molecule, and an application thereof in nucleic acid delivery. The structural formula of the cationic lipid molecule is represented by formula i. The invention further provides a cationic liposome, a lipid compound, a reagent, a kit, a preparation and a medicinal composition based on the cationic lipid molecule. The cationic lipid molecule has the advantages of simple synthesis process and good stability, and the cationic liposome has a high efficiency (characterized by high transfection efficiency) and a low toxicity, is stable and uniform, is easy to prepare, and can be used for transferring various cell lines. The cationic lipid molecule has excellent transitivity, and can efficiently deliver active substances (such as exemplary siRNA) omto cells (such as exemplary lung cancer cells), tissues and organs to achieve efficient regulation of the active substances. The problem that the toxicity and the transfer efficiency of cationic liposome existing in the prior art are low is solved.
Palladium-Catalyzed Decarboxylative Carbonylative Transformation of Benzyl Aryl Carbonates: Direct Synthesis of Aryl 2-Arylacetates
Xu, Jian-Xing,Wu, Xiao-Feng
supporting information, p. 5938 - 5941 (2018/09/21)
A procedure on palladium-catalyzed decarboxylative alkoxycarbonylation of carbonates for the synthesis of aryl 2-arylacetates has been developed. A broad range of aryl 2-arylacetates were obtained in good yields under mild conditions under a carbon monoxide atmosphere. Interestingly, other alcohols can be added as nucleophiles as well, and the corresponding esters were also obtained in good yields.
