- Synthesis of multifunctional PAMAM-aminoglycoside conjugates with enhanced transfection efficiency
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The development of multifunctional vectors for efficient and safe gene delivery is one of the major challenges for scientists working in the gene therapy field. In this context, we have designed a novel type of aminoglycoside-rich dendrimers with a defined structure based on polyamidoamine (PAMAM) in order to develop efficient, nontoxic gene delivery vehicles. Three different conjugates, i.e., PAMAM G4-neamine, -paromomycin, and -neomycin, were synthesized and characterized by nuclear magnetic resonance (NMR) and MALDI analysis. The conjugates were found to self-assemble electrostatically with plasmid DNA, and unlike neamine conjugate, each at its optimum showed increased gene delivery potency compared to PAMAM G4 dendrimer in three different cell lines, along with negligible cytotoxicity. These results all disclosed aminoglycosides as suitable functionalities for tailoring safe and efficient multifunctional gene delivery vectors.
- Ghilardi, Alessandra,Pezzoli, Daniele,Bellucci, Maria Cristina,Malloggi, Chiara,Negri, Armando,Sganappa, Aurora,Tedeschi, Gabriella,Candiani, Gabriele,Volonterio, Alessandro
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p. 1928 - 1936
(2014/01/06)
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- RNA binding compounds and uses thereof
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A method for determining whether a test compound binds to a large RNA target, comprising the steps of: (a) contacting the test compound with a pair of indicator molecules comprising (i) a fluorescent oxazolidinone or aminoglycoside reporter molecule and (ii) the large RNA target; and (b) measuring the fluorescence of reporter molecule in the presence of the test compound and comparing this value to the fluorescence of the reporter in the absence of the test compound. It has been found that large RNA molecule are advantageous in this type of binding assay.
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- Dehydroxylation of aminosugars
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Dehydroxylation of aminoglycoside antibiotics is carried out by halogenation of phosphorylated aminoglycoside antibiotics followed by reduction of thus halogenated antibiotics. The dehydroxylation process is entirely new and gives the final product in a high yield. The resulting deoxyaminoglycoside antibiotics are effective against microorganisms including aminoglycoside antiobiotics-resistant microorganisms.
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