title: Therapeutic oligonucleotides with polyethylene glycol modifications.
abstract: In the field of oligonucleotide drugs, the attachment of PEG is a well-established strategy to prevent enzymatic degradation and avoid renal elimination. Pegaptanib and other oligonucleotides in clinical development utilize the attachment of linear or branched high molecular weight PEG chains for increase of accumulation and duration of the effect after local or systemic application. The length of PEG chains is decisive for the pharmacokinetic and pharmacodynamic effects. Longer chains increase circulation times, but generally decrease gene-silencing efficiencies for antisense and siRNA agents and binding affinities for aptamers. Shorter chains are less efficient in preventing renal filtration, but have also less impact on the gene-silencing machinery and binding kinetics.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Vienna, Althanstraße 14, 1090 Vienna, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Winkler
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D009841:Oligonucleotides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D034741:RNA, Small Interfering / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D052157:Aptamers, Nucleotide; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; C495058:pegaptanib; D011092:Polyethylene Glycols