| A new platform for oligonucleotide delivery utilizing the PEG prodrug approach. | |
| | |
MedLine Citation:
|
PMID: 16029016 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The oligonucleotide (oligo, ODN), Genasense (GS), an ODN currently waiting for FDA approval, was chosen as a model and modified with a 5' or 3' aminohexyl functionality (1 and 4, respectively) using solid-state synthesis. These amino derivatives were reacted with different releasable PEGs (rPEGs). The in vitro results of the PEG-modified oligos (Table 1) clearly show a substantial increase in rat plasma half-life and enhanced stability against a variety of nucleases, especially the predominant nuclease (PEII) in mammals, which is the main source of oligo degradation in cells. The advantage of using a PEG prodrug approach was further demonstrated by the pharmacokinetic (PK) results, which exhibited much greater C(max), plasma half-life, and area under the curve (AUC) for 3 compared to unmodified GS. A key step in the synthesis of ODN prodrug conjugates with a dye label was also accomplished successfully by employing dihydropyran derivatives of alcohols and acids as orthogonal protecting groups during the synthesis. |
| | |
Authors:
|
Hong Zhao; Richard B Greenwald; Prasanna Reddy; Jing Xia; Ping Peng |
Related Documents
:
|
21137686 - Novel thione-thiol rearrangement of dithiocarbonic acid o-(2,2,6,6-tetramethylpiperidin... 1511066 - Biosynthesis of guanidinoacetic acid in isolated renal tubules. 15176826 - Synthesis and x-ray crystal structure of the dolabellaauricularia peptide dolastatin 18. 5283956 - Hormone-controlled synthesis of endoplasmic reticulum in barley aleurone cells. 567036 - Accumulation of 1-trans-2,3-epoxysuccinic acid and succinic acid by paecilomyces varioti. 1463786 - Reagent for introducing pyrene residues in oligonucleotides. |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Bioconjugate chemistry Volume: 16 ISSN: 1043-1802 ISO Abbreviation: Bioconjug. Chem. Publication Date: 2005 Jul-Aug |
Date Detail:
|
Created Date: 2005-07-20 Completed Date: 2005-11-30 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9010319 Medline TA: Bioconjug Chem Country: United States |
Other Details:
|
Languages: eng Pagination: 758-66 Citation Subset: IM |
Affiliation:
|
Enzon Pharmaceuticals Inc., 20 Kingsbridge Road, Piscataway, New Jersey 08854, USA. hong.zhao@enzon.com |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Chromatography, High Pressure Liquid Magnetic Resonance Spectroscopy Oligonucleotides / chemistry* Polyethylene Glycols / chemistry* Prodrugs / chemistry* Spectrometry, Mass, Electrospray Ionization Xanthenes / chemistry |
| Chemical | |
Reg. No./Substance:
|
0/Oligonucleotides; 0/Polyethylene Glycols; 0/Prodrugs; 0/Xanthenes; 82354-19-6/Texas red |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Development of a rhenium-186-labeled MAG3-conjugated bisphosphonate for the palliation of metastatic...
Next Document: Enzymatic degradation of liposome-grafted poly(hydroxyethyl L-glutamine).