| Synthesis and Characterization of Methylated Poly(L-histidine) to Control the Stability of its siRNA Polyion Complexes for RNAi. | |
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MedLine Citation:
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PMID: 22681572 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Poly(L-histidine) (PLH) with dimethyl imidazole groups has been synthesized as a pH-sensitive polypeptide to control the stability of its siRNA polyion complexes for RNAi. The resulting methylated PLH (PLH-Me) was water-soluble despite deprotonation of the imidazole groups at physiological pH, as determined by acid-base titration and solution turbidity measurement. Agarose gel retardation assay proved that the quaternary dimethyl imidazole groups worked as cationic groups to retain siRNA. The stability of the PLH-Me/siRNA complexes have depended on the content of hydrophobic groups, that is, tau/pai-methyl imidazole groups as well as deprotonated imidazole groups. The PLH-Me exhibited no significant cytotoxicity in spite of the existence of cationic dimethyl imidazole groups. By using PLH-Me as a pH-sensitive siRNA carrier, the PLH-Me/siRNA complexes mediated efficient siRNA delivery attributed to the dimethyl imidazole groups, and the gene silencing depended on the content balance among dimethyl, tau/pai-methyl, and unmodified imidazole groups. These results suggest that the PLH-Me to control the stability of siRNA polyion complexes enhanced the noncytotoxic siRNA delivery by optimizing the content balance of dimethyl, tau/pai-methyl, and unmodified imidazole groups. |
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Authors:
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Shoichiro Asayama; Takao Kumagai; Hiroyoshi Kawakami |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-6-10 |
Journal Detail:
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Title: Bioconjugate chemistry Volume: - ISSN: 1520-4812 ISO Abbreviation: - Publication Date: 2012 Jun |
Date Detail:
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Created Date: 2012-6-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9010319 Medline TA: Bioconjug Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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