Mimicry of Biological Macromolecules by Polyaromatic Anionic Compounds

Abstract

The preparation, characterization and biological properties of some polyanionic polymers are reported. These polymers are constructed with repeating phenol-based monomers. The anionic groups attached to the aromatic nucleus provide the basis for binding to basic domains of proteins. Scaf-*Author to whom correspondence should be addressed.at CARLETON UNIV on June 21, 2015 jbc.sagepub.com Downloaded from 318 fold flexibility permits the polyanionic polymers to adopt low energy conformations suitable for interacting with coagulation proteins and an anti-DNA monoclonal antibody. Structure activity relationships (SAR) and comparisons with aurintricarboxylic acid are described. The polymers doubled the clotting time in the APTT assay with value ranging from 10-1000 μg/mL. Binding to an anti-DNA monoclonal antibody occurred with ICso values of 0.3-5.0 μg/mL. INTRODUCTIOÑ

Modulation of fibroblast growth factor-2 receptor binding, dimerization, signaling, and angiogenic activity by a synthetic heparin-mimicking polyanionic compound.

“…The results of the present study show that a synthetic polyanionic aromatic compound (RG-13577, poly-4-hydroxyphenoxy acetic acid) is capable of inhibiting FGF-2-induced endothelial cell proliferation and microvessel formation. This compound mimics some of the functional properties of heparin, but exerts only ‫%1ف‬ of its anticoagulant activity (17). RG-13577 interacts directly with FGF-2 as demonstrated by its ability to inhibit the binding of 125 I-heparin to FGF-2.…”

“…Suramin, ATA, and RG-13577 contain a nondegradable backbone, while heparin/HS is sensitive to hydrolytic enzymes. Unlike ATA, whose polymeric structure is undefined (53), RG-13577 is characterized by a substantially ordered linear backbone (17).…”

“…Aromatic ring monomers were chosen and strong oxidizing reagents avoided so that the polymerization process with formaldehyde would yield substantially ordered and defined backbones (17). Using this approach, a series of polyanionic polymers was identified with repeating phenol-based monomers, including poly-4-hydroxyphenoxy acetic acid, hereby termed compound RG-13577, that mimics various effects of heparin.…”

“…In an attempt to identify potent mimetics of heparin/HS, acid-catalyzed polymerization of phenols and formaldehyde was used to synthesize negatively charged, nonsulfated polyanionic compounds (17). Aromatic ring monomers were chosen and strong oxidizing reagents avoided so that the polymerization process with formaldehyde would yield substantially ordered and defined backbones (17).…”

Antiproliferative activity to vascular smooth muscle cells and receptor binding of heparin-mimicking polyaromatic anionic compounds.

“…[ 125 I]NaI was obtained from Amersham. Compound RG-13577 (a polymer of 4-hydroxyphenoxyacetic acid and formaldehyde ammonium salt; M r ~58O0) (Fig 1), 14 C-labeled RG-13577 (25.6 jtCi/mg), and related compounds were synthesized and kindly provided by Rhone-Poulenc-Rorer Co. 19 […”