In Vitro Binding of Synthetic Acylated Lipid-Associating Peptides to High-Density Lipoproteins: Effect of Hydrophobicity

Gabriel Ponsin, Kerry Strong, Antonio M. Gotto, James T. Sparrow, Henry J. Pownall

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

To measure the effect of hydrophobicity on the binding of model apoproteins to lipoproteins, we synthesized a 15 amino acid lipid-associating peptide (LAP) with acyl chains of various lengths (0-18 carbons) bound to the N-terminal amino acid through a peptide bond. The acylated LAPs preferentially bound to high-density lipoprotein (HDL) and were activators of lecithin:cholesterol acyltransferase. Circular dichroic spectra indicated that the LAP association with phospholipid was accompanied by increased α-helical structure. The LAPs self-associated in solution as judged from tryptophan fluorescence analysis. These characteristics, which are comparable to those of apolipoprotein A-I, were strongly dependent upon the acyl chain length of the LAPs. The equilibrium constants (Keq) for the association of LAPs to reassembled HDL were measured by equilibrium dialysis at several temperatures. At 37°C, Keq increased by 3 orders of magnitude as the number of carbon units was increased from 0 to 16; there was a log-linear relationship between Keq and the acyl chain length. The free energy of association (ΔGa) decreased by a constant value for each methylene unit added to the acyl chain (0.35 kcal mol-1), clearly demonstrating a strict hydrophobic effect. This change of ΔGa was enthalpy rather than entropy driven. Our data show that, with all other parameters including putative α-helicity, sequence, and molecular weight being constant, the binding of a lipid-associating peptide to lipoprotein is governed by its hydrophobicity.

Original languageEnglish (US)
Pages (from-to)5337-5342
Number of pages6
JournalBiochemistry
Volume23
Issue number22
DOIs
StatePublished - Oct 1984

ASJC Scopus subject areas

  • Biochemistry

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