| Study of physico-chemical properties of novel highly sulfated, aromatic, mimetics of heparin and heparan sulfate. | |
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MedLine Citation:
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PMID: 19711446 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Heparin (H) and heparan sulfate (HS) play major roles in a number of biological processes. Yet, H/HS-based pharmaceutical agents are also associated with multiple adverse effects. This has led to the concept of designing noncarbohydrate, aromatic mimetics that modulate H/HS function. In this work, we study a library of synthetic, aromatic H/HS mimetics for their capillary electrophoretic profiles, the acid and base stability, and aqueous-organic partitioning property. The nonsugar H/HS mimetics exhibit electrophoretic properties similar to sulfated oligosaccharides suggesting that the mimetics can be rapidly and quantitatively analyzed. Stability studies show that the mimetics are essentially stable under neutral and basic conditions in a manner similar to the heparins, but are considerably unstable under acidic conditions in contrast to heparins. The measurement of partition coefficients show major differences within the sulfated mimetics as well as between the measured and calculated log P values. Understanding these physico-chemical properties is expected to have significant implications in the pharmaceutical development of this growing class of molecules. |
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Authors:
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Aiye Liang; Jay N Thakkar; Umesh R Desai |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of pharmaceutical sciences Volume: 99 ISSN: 1520-6017 ISO Abbreviation: J Pharm Sci Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-01-19 Completed Date: 2010-04-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985195R Medline TA: J Pharm Sci Country: United States |
Other Details:
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Languages: eng Pagination: 1207-16 Citation Subset: IM |
Copyright Information:
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2009 Wiley-Liss, Inc. and the American Pharmacists Association |
Affiliation:
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Department of Medicinal Chemistry, Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, Richmond, Virginia 23219, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Anticoagulants
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chemical synthesis,
chemistry* Chemistry, Pharmaceutical / methods Drug Design* Drug Stability Electrophoresis, Capillary / methods Heparin / analogs & derivatives, chemistry* Heparitin Sulfate / chemistry* Molecular Structure Physicochemical Processes* Polycyclic Hydrocarbons, Aromatic / chemical synthesis, chemistry* Solubility |
| Grant Support | |
ID/Acronym/Agency:
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HL069975/HL/NHLBI NIH HHS; HL090586/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anticoagulants; 0/Polycyclic Hydrocarbons, Aromatic; 9005-49-6/Heparin; 9050-30-0/Heparitin Sulfate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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