Efficient synthesis of diverse heterobifunctionalized clickable oligo(ethylene glycol) linkers: Potential applications in bioconjugation and targeted drug delivery

Goswami, Lalit N., Houston, Zachary H., Sarma, Saurav J., Jalisatgi, Satish S. and Hawthorne, M. Frederick (2013) Efficient synthesis of diverse heterobifunctionalized clickable oligo(ethylene glycol) linkers: Potential applications in bioconjugation and targeted drug delivery. Organic and Biomolecular Chemistry, 11 7: 1116-1126. doi:10.1039/c2ob26968f


Author Goswami, Lalit N.
Houston, Zachary H.
Sarma, Saurav J.
Jalisatgi, Satish S.
Hawthorne, M. Frederick
Title Efficient synthesis of diverse heterobifunctionalized clickable oligo(ethylene glycol) linkers: Potential applications in bioconjugation and targeted drug delivery
Journal name Organic and Biomolecular Chemistry   Check publisher's open access policy
ISSN 1477-0520
1477-0539
Publication date 2013-02-21
Year available 2013
Sub-type Article (original research)
DOI 10.1039/c2ob26968f
Open Access Status Not Open Access
Volume 11
Issue 7
Start page 1116
End page 1126
Total pages 11
Place of publication Cambridge, United Kingdom
Publisher Royal Society of Chemistry
Language eng
Abstract Herein we describe the sequential synthesis of a variety of azide-alkyne click chemistry-compatible heterobifunctional oligo(ethylene glycol) (OEG) linkers for bioconjugation chemistry applications. Synthesis of these bioorthogonal linkers was accomplished through desymmetrization of OEGs by conversion of one of the hydroxyl groups to either an alkyne or azido functionality. The remaining distal hydroxyl group on the OEGs was activated by either a 4-nitrophenyl carbonate or a mesylate (-OMs) group. The -OMs functional group served as a useful precursor to form a variety of heterobifunctionalized OEG linkers containing different highly reactive end groups, e.g., iodo, -NH2, -SH and maleimido, that were orthogonal to the alkyne or azido functional group. Also, the alkyne- and azide-terminated OEGs are useful for generating larger discrete poly(ethylene glycol) (PEG) linkers (e.g., PEG 16 and PEG24) by employing a Cu(i)-catalyzed 1,3-dipolar cycloaddition click reaction. The utility of these clickable heterobifunctional OEGs in bioconjugation chemistry was demonstrated by attachment of the integrin (αvβ3) receptor targeting peptide, cyclo-(Arg-Gly-Asp-d-Phe-Lys) (cRGfKD) and to the fluorescent probe sulfo-rhodamine B. The synthetic methodology presented herein is suitable for the large scale production of several novel heterobifunctionalized OEGs from readily available and inexpensive starting materials.
Keyword Chemistry, Organic
Chemistry
CHEMISTRY, ORGANIC
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID R21 CA114090
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Centre for Advanced Imaging Publications
 
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Created: Mon, 11 Aug 2014, 20:09:26 EST by Zach Houston on behalf of Centre for Advanced Imaging