Structural Characterization of a Serendipitously Discovered Bioactive Macromolecule, Lignin Sulfate

The herpes simplex virus-1 (HSV-1) utilizes cell-surface glycosaminoglycan, heparan sulfate, to gain entry into cells and cause infection. In a search for synthetic mimics of heparan sulfate to prevent HSV infection, we discovered potent inhibitory activity arising from sulfation of a monomeric flav...

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Bibliographic Details
Published in:Biomacromolecules 2005-09, Vol.6 (5), p.2822-2832
Main Authors: Raghuraman, Arjun, Tiwari, Vaibhav, Thakkar, Jay N, Gunnarsson, Gunnar T, Shukla, Deepak, Hindle, Michael, Desai, Umesh R
Format: Article
Language:English
Subjects:
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiviral agents
Applied sciences
Biocompatible Materials - chemistry
Biological and medical sciences
Centrifugation
Chromatography
Chromatography, High Pressure Liquid
Electrophoresis, Capillary
Electrophoresis, Polyacrylamide Gel
Exact sciences and technology
HeLa Cells
Heparitin Sulfate - chemistry
Herpes simplex virus 1
Herpesvirus 1, Human - metabolism
Humans
Inhibitory Concentration 50
Lignin - chemistry
Lignin and derivatives
Macromolecular Substances - chemistry
Magnetic Resonance Spectroscopy
Mass Spectrometry
Medical sciences
Models, Chemical
Natural polymers
Pharmacology. Drug treatments
Physicochemistry of polymers
Polymers - chemistry
Tannins - chemistry
Time Factors
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Summary:The herpes simplex virus-1 (HSV-1) utilizes cell-surface glycosaminoglycan, heparan sulfate, to gain entry into cells and cause infection. In a search for synthetic mimics of heparan sulfate to prevent HSV infection, we discovered potent inhibitory activity arising from sulfation of a monomeric flavonoid. Yet, detailed screening indicated that the sulfated flavonoid was completely inactive and the potent inhibitory activity arose from a macromolecular substance present in the parent flavonoid. The active principle was identified through a battery of biophysical and chemical analyses as a sulfated form of lignin, a three-dimensional network polymer composed of substituted phenylpropanoid monomers. Mass spectral analysis of the parent lignin and its sulfated derivative indicates the presence of p-coumaryl monomers interconnected through uncondensed β-O-4-linkages. Elemental analysis of lignin sulfate correlates primarily with a polymer of p-coumaryl alcohol containing one sulfate group. High-performance size exclusion chromatography shows a wide molecular weight distribution from 1.5 to 40 kDa suggesting significant polydispersity. Polyacrylamide gel electrophoresis (PAGE) analysis indicates a highly networked polymer that differs significantly from linear charged polymers with respect to its electrophoretic mobility. Overall, macromolecular lignin sulfate presents a multitude of substructures that can interact with biomolecules, including viral glycoproteins, using hydrophobic, hydrogen-bonding, and ionic forces. Thus, lignin sulfate represents a large number of interesting structures with potential medicinal benefits.
ISSN:1525-7797
1526-4602
DOI:10.1021/bm0503064