Antitubercular Studies. Heterocyclic Fatty Acids

Graef, Edith; Fredericksen, James M.; Burger, Alfred

doi:10.1021/jo01173a008

Cited by 18 publications

(2 citation statements)

References 13 publications

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“…Proprionic acid 22 9-(1-Ethylpropyl) 30 2-Ethylbutyric acid 18 9-Heptyl-20 Octanoic acid 18 9-Heptadecyl-? Stearic acid 23 9-(4-Hydroxyphenyl)-27 4-Hydroxybenzoic acid 24 9-Methyl-55 Acetic Acid Ethyl sebcyl chloride 25 9-Pentadecyl ? Palmitic acid 22 9-Phenyl 48 Benzoic acid 13 9-(1-Phenylethyl)-30 2-Phenylproprionic acid 18 -9-Proprionic acid 10 Succinic acid 23 9-Propyl ?…”

Section: Isolation and Synthesis Of Acridinementioning

confidence: 99%

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Glycan targeted gene delivery to the dendritic cell SIGN receptor

Anderson¹

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The 21 st century has been called the age of genomic medicine, yet gene therapy for medicinal use remains a theory. One reason that there are no safe and effective treatments for human disease is the lack of a vehicle capable of delivering genetic material to a specific target. In nature we observe gene pathology by viral vectors, which deliver their own genetic material to specific host cells efficient at spreading the viral blueprint throughout the organism.The aim of my research into gene therapy has been to develop a synthetic vector with the delivery capability of viral vectors found in nature. This includes the ability to protect genetic cargo from modification and degradation in vivo, target to a desired cell type within a specific tissue, facilitating absorption into the cell, and delivery to the nucleus, where expression of genetic material occurs.The goal of this thesis project was to synthesize a novel vector which would selectively target the dendritic cell SIGN receptor, mirroring the method of pathogens such as HIV, which target this receptor and subsequently the immune system, resulting in chronic infection.The vector we designed contains two major components, the high mannose Nglycan Man 9 GlcNAc 2 Asn, and a peptide composed of nine amino acids: four lysine spacing residues, four lysines derivatized with acridine on the epsilon amine of their side chains, and a cysteine for conjugation to the glycan. This compound, the Man 9 -AcrLys Glycopeptide, was engineered to intercalate into plasmid DNA via the acridine functional groups and to bind the DC-SIGN receptor through the glycan's mannose residues.The vehicle was tested in vitro in CHO cells bearing a recombinant DC-SIGN receptor in the context of luciferase reporter gene delivery. We found that under equal treatment conditions, DC-SIGN (+) CHO cells expressed more luciferase and were 100fold more luminescent than control DC-SIGN (-) CHO cells.My delivery method was further analyzed in a cell-sorting FACS experiment. I covalently labeled pGL3 reporter plasmid with a fluorophore, and transfected the CHO cells under typical transfection conditions. The experimental results confirmed preferential DC-SIGN mediated gene delivery. ACKNOWLEDGMENTSThank you, Dr. Rice, for your exceptional leadership and guidance throughout my graduate career. From the time of my first correspondence with the University of Iowa until the end, you made sure that I and the rest of my colleagues had a graduate experience which met and exceeded expectations.

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Section: Isolation and Synthesis Of Acridinementioning

confidence: 99%

“…Each polyplex was given 30 min to form at RT.DC-SIGN (+) CHO cells were treated with 30 μL of each polyplex in triplicate, and returned to the incubator. After incubation for 24 hr, the transfection media was removed, the cells were washed with 2 mL DPBS and lysed with 0.5 mL lysis buffer(25…”

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confidence: 99%