A NATURAL MOTIF APPROACH TO PROTEIN DESIGN - A SYNTHETIC LEUCINE-ZIPPER PEPTIDE MIMICS THE BIOLOGICAL FUNCTION OF THE PLATELET FACTOR 4 PROTEIN

The design of smaller functional mimics of large proteins has long bee n an important challenge. In this study we use the natural leucine zip per as a structural template to design a 31-residue peptide analog tha t mimics the function of the larger platelet factor 4 (PF4) protein. T he heparin binding activity of PF4 has been introduced into an unrelat ed leucine zipper sequence only by virtue of incorporating four lysine s of PF4, Circular dichroism and binding experiments have shown that t he designed leucine zipper peptide adopts a stable helical conformatio n and shows significant PF4-Iike heparin binding activity. These resul ts strongly suggest that the lysine residues play an important role in the binding of PF4 to heparin. The de novo generation of the PF4 func tion in a designed leucine zipper peptide demonstrates that the leucin e zipper motif is a useful scaffold for the design of functional pepti des and proteins. (C) 1997 Federation of European Biochemical Societie s.