Ja. Gazzara et al., INTERACTION OF CLASS-A AMPHIPATHIC HELICAL PEPTIDES WITH PHOSPHOLIPIDUNILAMELLAR VESICLES, Journal of lipid research, 38(10), 1997, pp. 2134-2146
The exchangeable apolipoproteins are important in determining the stru
cture/function properties of lipoproteins. These proteins typically co
ntain varying amounts of amphipathic helices. Five model peptides, 18A
, Ac-18A-NH2, Ac-18R-NH2, 37pA, and 37aA, have been designed to invest
igate variations of tile amphipathic alpha-helix structural motif on t
heir lipid-binding propel-ties. These include the 18-residue peptides,
18A and Ac-18A-NH2, examples of class it helices, and Ac-18K-NH2, whi
ch has the positions of acidic and basic residues interchanged relativ
e to 18A. Three larger peptides were also studied: 36A, a dimer of 18A
, 37pA and 37aA, dimers of 18A coupled by Pro (18A-Pro-18A) and hla (1
8A-Ala-18A), respectively. We report here the results of a thermodynam
ic characterization of the binding properties of these peptides to sma
ll unilamellar vesicles of POPC. Partition coefficients, K-p, were det
ermined by fluorescence spectroscopy and binding enthalpies, Delta H,
by titration calorimetry. These parameters were used to obtain the fre
e energies, Delta G(0), and entropies, Delta S degrees, of binding. Th
e results of this study indicate k(p) values on the order of 10(5), wi
th interactions being enthalpically but not entropically favored in al
l cases. The presence of positively charged residues at the interface
(18A and Ac-18A-NH3) enhances binding but has little effect on the ext
ent of bilayer penetration. The presence of tandem repeats decreases l
ipid affinities for these small, highly curried bilayers. Our results
are consistent with the idea that interaction appears to be confined l
argely to the surface, with some degree of penetration of the hydropho
bic face of the helix into the interior of the bilayer.