Modification of Thiol Functionalized Aptamers by Conjugation of Synthetic Polymers
Aptamers are known for their short in vivo circulating half-life and rapid renal clearance. Their conjugation to poly(ethylene glycol) (PEG) is a way to improve their residence in the body. Two aptamers (AptD and AptF), having a disulfide protected thiol modification on the 3′ end, have been conjuga...
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| Veröffentlicht in: | Bioconjugate chemistry 2010-01, Vol.21 (1), p.169-174 |
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| container_end_page | 174 |
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| container_title | Bioconjugate chemistry |
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| creator | Da Pieve, Chiara Williams, Paul Haddleton, David M Palmer, Richard M. J Missailidis, Sotiris |
| description | Aptamers are known for their short in vivo circulating half-life and rapid renal clearance. Their conjugation to poly(ethylene glycol) (PEG) is a way to improve their residence in the body. Two aptamers (AptD and AptF), having a disulfide protected thiol modification on the 3′ end, have been conjugated to maleimide activated PEGs of various molecular weights and structures (linear PEG20; branched PEG20 and 40; PolyPEG17, 40, and 60 kDa). The high yield coupling (70−80% in most of the cases) could be achieved using immobilized tris[2-carboxyethyl]phosphine hydrochloride (TCEP) as reducing agent at pH 4. The affinity of PEGylated AptD for its target was reduced by conjugation to linear PEG20 and branched PEG40, but not to branched PEG20 and PolyPEGs. This work demonstrates an alternative approach to PEGylation of aptamers, and that the effect of PEG on the affinity for the target varies according to the structure and conformation of the synthetic polymer. |
| doi_str_mv | 10.1021/bc900397s |
| format | Article |
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| ispartof | Bioconjugate chemistry, 2010-01, Vol.21 (1), p.169-174 |
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| language | eng |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | Aptamers, Nucleotide - chemistry Aptamers, Nucleotide - genetics Aptamers, Nucleotide - metabolism Aptamers, Nucleotide - pharmacokinetics Binding Sites Chemistry Drug Carriers - chemistry Effects Half-Life Hydrogen-Ion Concentration Kinetics Maleimides - chemistry Molecular Weight Mucin-1 - genetics Phosphines - chemistry Polyethylene glycol Polyethylene Glycols - chemistry Spectrometry, Fluorescence Sulfhydryl Compounds - chemistry |
| title | Modification of Thiol Functionalized Aptamers by Conjugation of Synthetic Polymers |
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