Journal article
Diversity-oriented chemical modification of heparin : Identification of charge-reduced N-acyl heparin derivatives having increased selectivity for heparin-binding proteins
Bioorganic & medicinal chemistry, Vol.14(7), pp.2300-2313
2006
DOI: 10.1016/j.bmc.2005.11.013
PMID: 16314105
Abstract
The diversity-oriented chemical modification of heparin is shown to afford charge-reduced heparin derivatives that possess increased selectivity for binding heparin-binding proteins. Variable N-desulfonation of heparin was employed to afford heparin fractions possessing varied levels of free amine. These N-desulfonated heparin fractions were selectively N-acylated with structurally diverse carboxylic acids using a parallel synthesis protocol to generate a library of 133 heparin-derived structures. Screening library members to compare affinity for heparin-binding proteins revealed unique heparin-derived structures possessing increased affinity and selectivity for individual heparin-binding proteins. Moreover, N-sulfo groups in heparin previously shown to be required for heparin to bind specific proteins have been replaced with structurally diverse non-anionic moieties to afford identification of charge-reduced heparin derivatives that bind these proteins with equivalent or increased affinity compared to unmodified heparin. The methods described here outline a process that we feel will be applicable to the systematic chemical modification of natural polyanionic polysaccharides and the preparation of synthetic oligosaccharides to identify charge-reduced high affinity ligands for heparin-binding proteins. © 2005 Elsevier Ltd. All rights reserved.
Details
- Title: Subtitle
- Diversity-oriented chemical modification of heparin : Identification of charge-reduced N-acyl heparin derivatives having increased selectivity for heparin-binding proteins
- Creators
- LIUSHENG Huang - University of IowaRobert J Kerns - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Bioorganic & medicinal chemistry, Vol.14(7), pp.2300-2313
- Publisher
- Elsevier Science
- DOI
- 10.1016/j.bmc.2005.11.013
- PMID
- 16314105
- ISSN
- 0968-0896
- eISSN
- 1464-3391
- Language
- English
- Date published
- 2006
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984365883602771
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