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A basic compositional requirement of agents having heparin-like cell-modulating activities

P B Weisz1, M M Joullié, C M Hunter

  • 1Department of Bioengineering, University of Pennsylvania, Philadelphia 19104, U.S.A.

Biochemical Pharmacology
|July 1, 1997
PubMed
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Molecular agents with high anionic sulfate density, like heparin, modulate cell behavior through electrostatic complexation. This critical parameter, not structural detail, drives diverse activities such as angiogenesis and viral protection.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Pharmacology

Background:

  • Heparin exhibits diverse cell-modulating activities.
  • Previous research highlighted heparin's complex structure and varied biological functions.

Purpose of the Study:

  • To identify the key molecular parameter responsible for heparin's cell-modulating activities.
  • To investigate the role of anionic group density in biological function using cyclodextrins as model compounds.

Main Methods:

  • Utilized compositionally simple, low molecular weight cyclodextrins.
  • Assessed cell-modulating activities including angiogenesis, endothelial proliferation, smooth muscle cell growth inhibition, and antiviral protection.
  • Performed physical chemical analyses to investigate complex formation.

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Main Results:

  • A minimum intramolecular density of neighboring anionic (sulfate) groups was identified as the critical factor.
  • This parameter governs diverse activities such as angiogenesis, endothelial proliferation, and viral protection.
  • Evidence supports multi-ionic complex formation between anionic and cationic sites.

Conclusions:

  • Cell-modulating activities are primarily dependent on anionic sulfate group density, not intricate structural details.
  • Molecular agents with critical anionic sulfate density (MACADs) function via ionic complexation with proteins, modifying their activities.
  • This mechanism explains heparinoid and other related agent functions in cell biology and medicine.