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Modification of thiol functionalized aptamers by conjugation of synthetic polymers

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Da Pieve, Chiara, Williams, Paul, Haddleton, David M., Palmer, Richard M. J. and Missailidis, Sotiris (2010) Modification of thiol functionalized aptamers by conjugation of synthetic polymers. Bioconjugate Chemistry, Vol.21 (No.1). pp. 169-174. doi:10.1021/bc900397s

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Official URL: http://dx.doi.org/10.1021/bc900397s

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Abstract

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 oil 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 Iris[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 oil the affinity for the target varies according to the structure and conformation of the synthetic polymer.

Item Type: Journal Article
Subjects: Q Science > QD Chemistry
Divisions: Faculty of Science, Engineering and Medicine > Science > Chemistry
Journal or Publication Title: Bioconjugate Chemistry
Publisher: American Chemical Society
ISSN: 1043-1802
Official Date: January 2010
Dates:
DateEvent
January 2010Published
Volume: Vol.21
Number: No.1
Number of Pages: 6
Page Range: pp. 169-174
DOI: 10.1021/bc900397s
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Funder: Breast Cancer Campaign

Data sourced from Thomson Reuters' Web of Knowledge

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