New Approaches for the Preparation of Hydrophobic Heparin Derivatives
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Authors
Liu, Jian
Pervin, Azra
Gallo, Cindy M.
Desai, Umesh R.
Van Gorp, Cornelius L.
Linhardt, Robert J.
Issue Date
1994-01-01
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
A heparin derivative sufficiently lipophilic to be bound to plastics, forming blood-compatible supports, or to be used as an anticoagulant by transdermal or oral routes would be of great pharmaceutical interest. For such applications, the functional groups within heparin's antithrombin III binding site, responsible for its anticoagulant activity, cannot be modified. Chemistry is described in which lipophilic substituents were attached to the reducing termini of heparin chains. Substituents introduced at this position had a minimal effect on the antithrombin III binding sites found in heparin's interior. These derivatives, with enhanced hydrophobicities, were prepared using two distinctly different approaches. First, octyl isocyanate and octadecyl isocyanate were coupled to the core peptide of peptidoglycan heparin to form octyl- and octadecyl-peptidoglycan heparin. These octyl- and octadecyl-peptidoglycan heparins were then purified by hydrophobic interaction chromatography on phenyl-Sepharose CL-4B, demonstrating their enhanced hydrophobicities. Second, the lipophilic acyl hydrazides of various long chain fatty acids were coupled to heparin's reducing end. Caprylic (C8), capric (C10), lauric (C12), and stearic (C18) hydrazide derivatives of heparin were prepared using this approach. Only the stearyl hydrazide derivative of heparin showed a measurable increase in lipophilicity. This result demonstrated that a single small linear C8, C10, or C12 aliphatic chain was ineffective in enhancing the hydrophobicity of the highly negative, polyanionic heparin molecule. Two lipophilic chains, lauryl (C12) and stearyl (C18), were then coupled to a single heparin chain, resulting in a heparin derivative having enhanced hydrophobicity. All the heparin derivatives prepared in this study maintained some of their anticoagulant activity.
Description
Journal of Pharmaceutical Science , 83, 1034-1039
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
New Approaches for the Preparation of Hydrophobic Heparin Derivatives, J. Liu, A. Pervin, C. M. Gallo, U.R. Desai, C.L. VanGorp, R.J. Linhardt, Journal of Pharmaceutical Science , 83, 1034-1039, 1994.
Publisher
Terms of Use
Journal
Volume
Issue
PubMed ID
DOI
ISSN
15206017
223549
223549