The location of α‐tocopherol and α‐tocopheryl acetate in the membrane has been a subject of considerable interest, not only because of their relevant physiological function, but also for understanding their interaction with the phospholipids. We have examined this question by using reconstituted systems including dipalmitoyl‐glycerophosphocholine multibilayer vesicles to which α‐tocopherol and α‐tocopheryl acetate were incorporated. Differential scanning microcalorimetry measurements showed that both compounds were capable of modifying the thermotropic properties of the pure phospholipid, so that the pretransition disappears at low concentrations of these terpenoid molecules. The enthalpy corresponding to the main transition decreases as the concentration of α‐tocopherol increases and the transition peak is progressively shifted to lower temperatures. α‐Tocopheryl acetate gave the same type of effect but less marked than in the case of α‐tocopherol. Fourier‐transform infrared spectroscopic measurements were also made on these systems and the temperature dependence of the infrared spectra was studied. A comparison of the spectroscopic data showed that, in agreement with the calorimetric results, α‐tocopherol remarkably perturbs the thermotropic phase transition of dipalmitoylglycerophos‐phocholine. It was concluded from a study of the CH₂ stretching bands that α‐tocopherol induced changes in frequency and in bandwidth parameters. However, the changes in frequency and bandwidth with respect to temperature are not concerted; this is a consequence of the existence of more than one phase in the presence of α‐tocopherol. From the study of the CH₂ scissoring band, it was concluded that α‐tocopherol disrupts the acyl chain packing present in pure dipalmitoylglycerophosphocholine below the onset temperature of the gel‐to‐liquid‐crystal transition. The effect of α‐tocopheryl acetate is of a similar type of that of α‐tocopherol but weaker with respect to these stretching and scissoring CH₂ bands. Spectral changes were also found in the C=O stretching mode of the phospholipid in the presence of α‐tocopherol and these changes were attributed to perturbations in the C1‐C2 bonds of sn‐2‐acyl chains of the phospholipid. These effects were much weaker in the case of α‐tocopheryl acetate; it is suggested that this may be due to a specific interaction between α‐tocopherol and the polar region of the phospholipid. This interaction seems to be absent in the systems containing α‐tocopheryl acetate. The different locations in the membrane of α‐tocopherol and α‐tocopheryl acetate that can be inferred from these results are discussed.

We have identified the membrane-active regions of the severe acute respiratory syndrome coronavirus (SARS CoV) spike glycoprotein by determining the effect on model membrane integrity of a 16/18-mer SARS CoV spike glycoprotein peptide library. By monitoring the effect of this peptide library on membrane leakage in model membranes, we have identified three regions on the SARS CoV spike glycoprotein with membrane-interacting capabilities: region 1, located immediately upstream of heptad repeat 1 (HR1) and suggested to be the fusion peptide; region 2, located between HR1 and HR2, which would be analogous to the loop domain of human immunodeficiency virus type 1; and region 3, which would correspond to the pretransmembrane region. The identification of these membrane-active regions, which are capable of modifying the biophysical properties of phospholipid membranes, supports their direct role in SARS CoV-mediated membrane fusion, as well as facilitating the future development of SARS CoV entry inhibitors.