Fintan steele biography template
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- Publication number
- US6204248B1 US6204248B1US09/457,642US45764299AUS6204248B1US 6204248 B1US6204248 B1US 6204248B1US 45764299 AUS45764299 AUS 45764299AUS 6204248 B1US6204248 B1US 6204248B1
- Authority
- US
- United States
- Prior art keywords
- glutathione
- gsh
- cells
- cell
- redox
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
- Application number
- US09/457,642
- Inventor
- Harry B. Demopoulos
- Myron L. Seligman
- Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
- ANTIOXIDANT PHAMACEUTICALS CORP
- Molecular Defenses Holdings LLC
- Original Assignee
- Antioxidant Pharmaceuticals Corp
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- Filin
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Significance
Aptamers are now used ubiquitously as binding agents for a broad range of applications. Natural (unmodified) DNA and RNA aptamers have considerably less chemical diversity than protein-based ligands such as antibodies, limiting their utility. Aptamers possessing a single chemical modification have helped bridge this diversity gap. We report the selection and identification of aptamers with two diversity-enhancing chemical modifications that bind and inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9), a representative human therapeutic protein target. The addition of a second modification, especially in certain pairwise combinations, resulted in significant improvements in affinity, ligand efficiency, epitope coverage, metabolic stability, and inhibitory activity. Extensively chemically functionalized aptamers have the potential to become the next generation of nucleic-acid–based ligands.
Keywords: SELEX, modified aptamer, PCSK9, SOMAmer, PSMA
Abstract
The nucleobases comprising DNA and RNA aptamers provide considerably less chemical diversity than protein-based ligands, limiting their versatility. The introduction of novel functional groups at just one of the four bases in modified aptamers has recently led to dramatic improvement in the success r
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