Document Detail


Synthesis and Characterization of Methylated Poly(L-histidine) to Control the Stability of its siRNA Polyion Complexes for RNAi.
MedLine Citation:
PMID:  22681572     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Shoichiro Asayama; Takao Kumagai; Hiroyoshi Kawakami
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-10
Journal Detail:
Title:  Bioconjugate chemistry     Volume:  -     ISSN:  1520-4812     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9010319     Medline TA:  Bioconjug Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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