SYNTHETIC MODEL PEPTIDES FOR APOLIPOPROTEINS .1. DESIGN AND PROPERTIES OF SYNTHETIC MODEL PEPTIDES FOR THE AMPHIPATHIC HELICES OF THE PLASMA APOLIPOPROTEINS
R. Brasseur et al., SYNTHETIC MODEL PEPTIDES FOR APOLIPOPROTEINS .1. DESIGN AND PROPERTIES OF SYNTHETIC MODEL PEPTIDES FOR THE AMPHIPATHIC HELICES OF THE PLASMA APOLIPOPROTEINS, Biochimica et biophysica acta, 1170(1), 1993, pp. 1-7
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.