Importance of the spatial display of charged residues in heparin-peptide interactions.
Many studies have examined consensus sequences required for protein-glycosaminoglycan interactions. Through the synthesis of helical heparin binding peptides, this study probes the relationship between spatial arrangement of positive charge and heparin binding affinity. Peptides with a linear distribution of positive charge along one face of the alpha-helix had the highest affinity for heparin. Moving the basic residues away from a single face resulted in drastic changes in heparin binding affinity of up to three orders of magnitude. These findings demonstrate that amino acid sequences, different from the known heparin binding consensus sequences, will form high affinity protein-heparin binding interactions when the charged residues are aligned linearly.
Rullo
Anthony
A
Department of Chemistry, University of Toronto, Toronto, ON, Canada.
Nitz
Mark
M
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics; D017433:Protein Structure, Secondary
D000596:Amino Acids; D010455:Peptides; D006493:Heparin