Formulation of highly soluble poly(ethylene glycol)-peptide DNA condensates
dc.contributor.author | Kwok, Kai Y. | en_US |
dc.contributor.author | Mckenzie, Donald L. | en_US |
dc.contributor.author | Evers, David L. | en_US |
dc.contributor.author | Rice, Kevin G. | en_US |
dc.date.accessioned | 2006-04-19T13:36:59Z | |
dc.date.available | 2006-04-19T13:36:59Z | |
dc.date.issued | 1999-10 | en_US |
dc.identifier.citation | Kwok, Kai Y.; Mckenzie, Donald L.; Evers, David L.; Rice, Kevin G. (1999)."Formulation of highly soluble poly(ethylene glycol)-peptide DNA condensates." Journal of Pharmaceutical Sciences 88(10): 996-1003. <http://hdl.handle.net/2027.42/34495> | en_US |
dc.identifier.issn | 0022-3549 | en_US |
dc.identifier.issn | 1520-6017 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/34495 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=10514346&dopt=citation | en_US |
dc.description.abstract | Two poly(ethylene glycol) (PEG)-peptides were synthesized and tested for their ability to bind to plasmid DNA and form soluble DNA condensates with reduced spontaneous gene expression. PEG-vinyl sulfone or PEG-orthopyridyl disulfide were reacted with the sulfhydryl of Cys-Trp-Lys 18 (CWK 18 ) resulting in the formation of nonreducible (PEG-VS-CWK 18 ) and reducible (PEG-SS-CWK 18 ) PEG- peptides. Both PEG-peptides were prepared on a micromole scale, purified by RP-HPLC in >80% yield, and characterized by 1H NMR and MALDI-TOF. PEG-peptides bound to plasmid DNA with an apparent affinity that was equivalent to alkylated (Alk)CWK 18 , resulting in DNA condensates with a mean diameter of 80–90 nm and ζ (zeta) potential of +10 mV. The particle size of PEG-peptide DNA condensates was constant throughout the DNA concentration range of 0.05–2 mg/mL, indicating these to be approximately 20-fold more soluble than AlkCWK 18 DNA condensates. The spontaneous gene transfer to HepG2 cells mediated by PEG-VS-CWK 18 DNA conden- sates was over two orders of magnitude lower than PEG-SS-CWK 18 DNA condensates and three orders of magnitude lower than AlkCWK 18 DNA condensates. PEG-VS-CWK 18 efficiently blocked in vitro gene transfer by reducing cell uptake. The results indicate that a high loading density of PEG on DNA is necessary to achieve highly soluble DNA condensates that reduce spontaneous in vitro gene transfer by blocking nonspecific uptake by HepG2 cells. These two properties are important for developing targeted gene delivery systems to be used in vivo. | en_US |
dc.format.extent | 122587 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | John Wiley & Sons, Inc. | en_US |
dc.subject.other | Chemistry | en_US |
dc.subject.other | Food Science, Agricultural, Medicinal and Pharmaceutical Chemistry | en_US |
dc.title | Formulation of highly soluble poly(ethylene glycol)-peptide DNA condensates | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Pharmacy and Pharmacology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Divisions of Pharmaceutics and Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065. | en_US |
dc.contributor.affiliationum | Divisions of Pharmaceutics and Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065. | en_US |
dc.contributor.affiliationum | Divisions of Pharmaceutics and Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065. | en_US |
dc.contributor.affiliationum | Divisions of Pharmaceutics and Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065. ; Divisions of Pharmaceutics and Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065. | en_US |
dc.identifier.pmid | 10514346 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/34495/1/10_ftp.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1002/(ISSN)1520-6017 | en_US |
dc.identifier.source | Journal of Pharmaceutical Sciences | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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