A Combinatorial Approach to the Discovery of Efficient Cationic Peptoid Reagents for Gene Delivery
A family of N-substituted glycine oligomers (peptoids) of defined length and sequence are shown to condense plasmid DNA into small particles, protect it from nuclease degradation, and efficiently mediate the transfection of several cell lines. The oligomers were discovered by screening a combinatori...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1998-02, Vol.95 (4), p.1517-1522 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Murphy, John E. Uno, Tetsuo Hamer, Janice D. Cohen, Fred E. Dwarki, Varavani Zuckermann, Ronald N. |
| description | A family of N-substituted glycine oligomers (peptoids) of defined length and sequence are shown to condense plasmid DNA into small particles, protect it from nuclease degradation, and efficiently mediate the transfection of several cell lines. The oligomers were discovered by screening a combinatorial library of cationic peptoids that varied in length, density of charge, side-chain shape, and hydrophobicity. Transfection activity and peptoid-DNA complex formation are shown to be highly dependent on the peptoid structure. The most active peptoid is a 36-mer that contains 12 cationic aminoethyl side chains. This molecule can be synthesized efficiently from readily available building blocks. The peptoid condenses plasmid DNA into uniform particles 50-100 nm in diameter and mediates the transfection of a number of cell lines with efficiencies greater than or comparable to DMRIE-C, Lipofectin, and Lipofectamine. Unlike many cationic lipids, peptoids are capable of working in the presence of serum. |
| doi_str_mv | 10.1073/pnas.95.4.1517 |
| format | Article |
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The oligomers were discovered by screening a combinatorial library of cationic peptoids that varied in length, density of charge, side-chain shape, and hydrophobicity. Transfection activity and peptoid-DNA complex formation are shown to be highly dependent on the peptoid structure. The most active peptoid is a 36-mer that contains 12 cationic aminoethyl side chains. This molecule can be synthesized efficiently from readily available building blocks. The peptoid condenses plasmid DNA into uniform particles 50-100 nm in diameter and mediates the transfection of a number of cell lines with efficiencies greater than or comparable to DMRIE-C, Lipofectin, and Lipofectamine. 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Unlike many cationic lipids, peptoids are capable of working in the presence of serum.</description><subject>3T3 Cells</subject><subject>Animals</subject><subject>Biochemistry</subject><subject>Biological Sciences</subject><subject>Cations</subject><subject>Cell Line</subject><subject>Cell lines</subject><subject>Chloroquine - chemistry</subject><subject>COS Cells</subject><subject>Culture Media</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Gene Transfer Techniques</subject><subject>Genes</subject><subject>Glycine - analogs & derivatives</subject><subject>Humans</subject><subject>Lipids</subject><subject>Mice</subject><subject>NIH 3T3 cells</subject><subject>Oligomers</subject><subject>Peptide Library</subject><subject>Peptides</subject><subject>Peptoids</subject><subject>Physical Sciences</subject><subject>Plasmids</subject><subject>Polymers</subject><subject>Reagents</subject><subject>Transfection</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks-L1DAYhoso67h69SAIwcPeWr-0-dGAl2FcV2FBkb2HNE12MnSamqTL7n9vygzD6EFPObzPk-TLm6J4i6HCwJuP06hiJWhFKkwxf1asMAhcMiLgebECqHnZkpq8LF7FuAMAQVu4KC4EYRQIXxXdGm38vnOjSj44NaD1NAWv9BYlj9LWoM8uav9gwhPyFl1b67QzY0IblZwfnUY_zJS869FPo-5zEJH1Ad2YMZtmcIv4unhh1RDNm-N6Wdx9ub7bfC1vv99826xvS80wS2XfE0MbzhthFa7rGlqGe9YR0itlFOM97nELoC2zTHWMa8qazpoMMA0dbi6LT4dtp7nbm17nywQ1yCm4vQpP0isn_0xGt5X3_kFiARyyfnXUg_81m5jkPk9uhkGNxs9RcsFawWj7XxCzmgpBeQY__AXu_BzG_ASyBty0LZDl2OoA6eBjDMaeLoxBLgXLpWApqCRyKTgL78_HPOHHRs_yxTulZ_7Vv3Jp52FI5jFl8N0B3MX8NU4kIQ2mzW82VsNC</recordid><startdate>19980217</startdate><enddate>19980217</enddate><creator>Murphy, John E.</creator><creator>Uno, Tetsuo</creator><creator>Hamer, Janice D.</creator><creator>Cohen, Fred E.</creator><creator>Dwarki, Varavani</creator><creator>Zuckermann, Ronald N.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><general>National Academy of Sciences</general><general>The National Academy of Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7QO</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19980217</creationdate><title>A Combinatorial Approach to the Discovery of Efficient Cationic Peptoid Reagents for Gene Delivery</title><author>Murphy, John E. ; 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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1998-02, Vol.95 (4), p.1517-1522 |
| issn | 0027-8424 1091-6490 |
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| source | MEDLINE; JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | 3T3 Cells Animals Biochemistry Biological Sciences Cations Cell Line Cell lines Chloroquine - chemistry COS Cells Culture Media Deoxyribonucleic acid DNA Gene Transfer Techniques Genes Glycine - analogs & derivatives Humans Lipids Mice NIH 3T3 cells Oligomers Peptide Library Peptides Peptoids Physical Sciences Plasmids Polymers Reagents Transfection |
| title | A Combinatorial Approach to the Discovery of Efficient Cationic Peptoid Reagents for Gene Delivery |
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