| Poly(N-acryl amino acids): a new class of biologically active polyanions. | |
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MedLine Citation:
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PMID: 10891119 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Poly(N-acryl amino acids) bearing side groups with a lipophilic character or having charged functional groups (i.e. -NH(2), -COOH, -SH, -OH, and phenols) were synthesized from the radical polymerization of N-acryl amino acid monomers. Monomers were prepared from the reaction of acryloyl chloride and amino acid esters in dry solvents. Polymers of a broad molecular weight ranging from 3 000 to 60 000 Da were obtained. The polymers were optically active, and their structures were confirmed by (1)H NMR and IR spectra and elemental analysis. Hydroxyl-containing polymers were sulfated in high conversion yields by SO(3)/pyridine complex. The newly synthesized linear homopolyanions were tested for heparin-like activities: (i) inhibition of heparanase enzyme, (ii) release of basic fibroblast growth factor (bFGF) from the extracellular matrix (ECM), and (iii) inhibition of smooth muscle cell (SMC) proliferation. Polymers based on tyrosine and leucine were highly active in all three tests (microgram level). Polymers based on phenylalanine, tert-leucine, and proline were active as heparanase inhibitors and FGF release, and polymers of trans-hydroxyproline, glycine, and serine were active only as heparanase inhibitors. The polymer of cis-hydroxyproline was inactive. It was found that a net anionic charge (i.e. carboxylic acid) is essential for biological activity. Thus, methyl ester derivatives of the active polymers, zwitterionic amino acid dependent groups (lysine, histidine), and decarboxylated amino acids (tyramine, ethanolamine) were inactive. The above active polymers did not exhibit anticoagulation activity which is considered the main limitation of heparin and heparinomimetics for clinical use. These synthetic poly(N-acryl amino acids) may have potential use in the inhibition of heparanase-mediated degradation of basement membranes associated with tumor metastasis, inflammation, and autoimmunity. |
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Authors:
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A Bentolila; I Vlodavsky; R Ishai-Michaeli; O Kovalchuk; C Haloun; A J Domb |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 43 ISSN: 0022-2623 ISO Abbreviation: J. Med. Chem. Publication Date: 2000 Jun |
Date Detail:
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Created Date: 2000-07-27 Completed Date: 2000-07-27 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 2591-600 Citation Subset: IM |
Affiliation:
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Department of Medicinal Chemistry, School of Pharmacy, The Hebrew University of Jerusalem, Israel. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acrylic Resins
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chemical synthesis*,
chemistry,
pharmacology Amino Acids / chemical synthesis*, chemistry, pharmacology Animals Anions Anticoagulants / chemical synthesis, chemistry, pharmacology Cattle Cell Division / drug effects Cells, Cultured Enzyme Inhibitors / chemical synthesis*, chemistry, pharmacology Extracellular Matrix / metabolism Fibroblast Growth Factor 2 / metabolism Heparin / chemistry, pharmacology Heparin Lyase / antagonists & inhibitors Humans Magnetic Resonance Spectroscopy Molecular Weight Muscle, Smooth, Vascular / cytology, drug effects Spectrophotometry, Infrared Structure-Activity Relationship |
| Chemical | |
Reg. No./Substance:
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0/Acrylic Resins; 0/Amino Acids; 0/Anions; 0/Anticoagulants; 0/Enzyme Inhibitors; 103107-01-3/Fibroblast Growth Factor 2; 9003-05-8/polyacrylamide; 9005-49-6/Heparin; EC 4.2.2.7/Heparin Lyase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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