SYNTHETIC MODEL PEPTIDES FOR APOLIPOPROTEINS .1. DESIGN AND PROPERTIES OF SYNTHETIC MODEL PEPTIDES FOR THE AMPHIPATHIC HELICES OF THE PLASMA APOLIPOPROTEINS

Amphipathic helical peptides are the lipid-binding motives of the plas ma apolipoproteins, and synthetic peptide analogs have been used to un ravel the mechanism of lipid association within this class of proteins . Hydrophobic interactions between the apolar amino acid residues belo nging to the hydrophobic face of the amphipathic helices and the lipid s are the major driving forces in the peptide-lipid association to for m discoidal complexes. Ionic interactions and salt bridge formation be tween contiguous peptide chains in the complex can, however, contribut e to the overall stability of the lipid-protein particle. This was stu died by designing peptide analogs to the helical repeats of the apolip oproteins with variable degrees of salt bridge formation between adjac ent peptide chains. The most stable conformation for pairs of syntheti c peptides was calculated by energy minimisation together with the ene rgy of interaction between peptides. The sequence of the peptides was derived from that of the 18A peptide synthesized by Segrest et al., an d the theoretical calculations confirmed that ionic interactions betwe en residues close to each other, along the edge of two adjacent anti-p arallel peptides, can significantly contribute towards the stability o f a peptide-phospholipid complex.