The Antiviral Peptide Carbobenzoxy-D-phenylalanyl-L-phenylalanylglycine Changes the Average Conformation of Phospholipids in Membranes

Document Type




Publication Date



American Chemical Society

Source Publication


Source ISSN



The influence of the antiviral peptide, carbobenzoxy-D-phenylalanyl-L-phenylalanylglycine (ZfFG), on the average conformation of phosphatidylcholine in hydrated bilayers was investigated with multinuclear solid state magnetic resonance (NMR). Phosphatidylcholine was specifically deuterated (separately) in the choline N-methyls, the α and β positions of the choline, the C2 carbon of the acyl chains, and at all the carbons of the acyl chains of the phosphatidylcholine. Phosphatidylcholine was also synthesized with the carbonyl carbons of the ester bonds between the glycerol and the hydrocarbon chains enriched in 13C. 2H NMR of the phosphatidylcholine perdeuterated in the acyl chains showed a loss of intensity from the deuteriums with the largest quadrupole splitting in the presence of ZfFG, while the remainder of the powder pattern was largely unaffected. The phosphatidylcholine specifically deuterated at the C2 carbon (representative of the C-D bonds giving rise to the largest quadrupole splittings) showed the same loss of intensity suggesting changes in the phospholipid conformation and conformational dynamics near the glycerol. Analysis of the powder patters in the 13C NMR spectrum of phosphatidylcholine labeled with the 13C in the carbonyl carbons revealed a significant change in the average orientation of the sn-1 carbonyl due to the presence of the ZfFG and no change in the sn-2 carbonyl orientation. Changes in the headgroup conformation, as detected by 2H NMR of the deuteriums in the α and β methylenes of the choline headgroup and 31P NMR of the phosphate segment, reflected the electrostatic nature of the interaction of the carboxyl of ZfFG with phosphatidylcholine bilayers. No significant effect was observed from the deuteriums in the N-methyls of the choline. From these data it was concluded that phosphatidylcholine had access to more than one conformation around the glycerol segment of the molecule in a bilayer. In the absence of ZfFG, the two carbonyls are inequivalent in their orientation. The antiviral peptide ZfFG favored a conformation in which the average orientations of the two ester carbonyls (with respect to the axis of rotation diffusion) were approximately equivalent. This altered phospholipid conformation may be the source of the differences in phospholipid packing observed in the presence of the antiviral compound. The loss of apparent 2H NMR intensity was likely due to the dynamics (on the time scale of 10-5 s) of the interchange between the (at least) two conformations adopted by the phosphatidylcholine in the presence of ZfFG.


Biochemistry, Vol. 32, No. 45 (November 1993): 12197-12202. DOI.