The interaction between heparin and polylysine: a circular dichroism and molecular modelling study.
The sulfated polysaccharide heparin interacts with both poly-L- and poly-D-lysine, promoting the alpha-helix conformation in the polypeptide. Chemically modified heparins in which one of the three sulfate groups per disaccharide has been removed form the same type of complex with poly-L-lysine; when two of the three sulfate groups are removed this property is lost. Heparin oligosaccharides as small as the octasaccharide can still promote alpha-helix in poly-L-lysine; the hexa- and tetrasaccharides do not, but they do disturb to a lesser extent the dynamic conformation equilibrium associated with poly-L-lysine at pH7 (22 degrees C). A three-dimensional structure for the heparin/polylysine complex is proposed in which the helical heparin molecule and the alpha-helical polypeptide are side-by-side, not intertwining. The regular periodicity of sulfate group clusters along one side of the polysaccharide chain matches the periodicity of the polypeptide alpha-helix, allowing electrostatic interactions every three peptide turns between a heparin sulfate cluster and a zeta-amino group of the polylysine. The heparin octasaccharide is the smallest even-numbered oligosaccharide long enough for two such interactions to take place.
Mulloy
B
B
National Institute for Biological Standards and Control, South Mimms, Potters Bar, Hertfordshire, UK.
Crane
D T
DT
Drake
A F
AF
Davies
D B
DB
D002942:Circular Dichroism; D004347:Drug Interactions; D006493:Heparin / Q000494:pharmacology*; D008958:Models, Molecular; D009844:Oligosaccharides; D011107:Polylysine / Q000494:pharmacology*
D009844:Oligosaccharides; D011107:Polylysine; D006493:Heparin