Effect of daptomycin on the barotropic behavior of dioleoylphosphatidylglycerol: An infrared spectroscopic investigation

According to our infrared spectra, the pressure-induced liquid-crystal to gel transition of dioleoylphosphatidylglycerol (DOPG) involves a conformational change making the glycerol C-sn-1-C-sn-2 bond more parallel to the bilayer surface and resulting in increased carbonyl groups hydrogen bonding. This conformational change allows a more compact packing of the cis unsaturated acyl chains. The lipopeptide daptomycin, at lipid/daptomycin molar ratios of 4:1, impedes the DOPG conformational change and induces an increase of the transition pressure from 5.5 (pure lipid) to 6.8 kbar and a higher disorder in the gel slate. The analogue (LY298862) of daptomycin containing a myristoyl instead of a decanoyl chain shifts the phase transition to 7.8 kbar at the same molar ratio and reduces more efficiently the lipid conformational change. The lipopeptide hydrocarbon chain length is thus a critical parameter in the modulation of the physical effects of this type of compounds, often used as antibiotics.