The interaction between heparin and polylysine: a circular dichroism and molecular modelling study

Area of Science:

• Biochemistry
• Polymer Science
• Structural Biology

Background:

• Heparin is a sulfated polysaccharide known for its biological activities.
• Polypeptides like poly-L-lysine can adopt various conformations, including alpha-helix.
• Understanding molecular interactions is crucial for drug development and biomaterial design.

Purpose of the Study:

• To investigate the interaction between heparin and poly-L-lysine.
• To determine the structural requirements for heparin-induced alpha-helix formation in poly-L-lysine.
• To elucidate the three-dimensional structure of the heparin/polylysine complex.

Main Methods:

• Chemical modification of heparin to remove sulfate groups.
• Study of heparin oligosaccharides of varying lengths (octasaccharide, hexasaccharide, tetrasaccharide).
• Conformational analysis of poly-L-lysine in the presence of heparin and its derivatives.
• Proposal of a three-dimensional structural model for the complex.

Main Results:

• Heparin promotes alpha-helix formation in both poly-L- and poly-D-lysine.
• Removal of one sulfate group per disaccharide did not abolish this property, but removal of two did.
• Heparin oligosaccharides down to the octasaccharide retained the ability to promote alpha-helix formation.
• The octasaccharide was the smallest even-numbered oligosaccharide capable of facilitating two specific electrostatic interactions.

Conclusions:

• The specific arrangement and number of sulfate groups on heparin are critical for inducing alpha-helix conformation in poly-L-lysine.
• A side-by-side, non-intertwining model is proposed for the heparin/polylysine complex, driven by electrostatic interactions between heparin sulfate clusters and polylysine.
• The heparin octasaccharide represents the minimum length for effective complex formation due to its capacity for two key interactions.