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

Authors

Philip L. Yeagle, State University of New York at BuffaloFollow
Andrew R. Dentino, Marquette UniversityFollow
Frazer T. Smith, State University of New York at Buffalo
Paul Spooner, University of Oxford
Anthony Watts, University of Oxford

Document Type

Article

Language

eng

Publication Date

11-1993

Publisher

American Chemical Society

Source Publication

Biochemistry

Source ISSN

0006-2960

Abstract

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.

Comments

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

Recommended Citation

Yeagle, Philip L.; Dentino, Andrew R.; Smith, Frazer T.; Spooner, Paul; and Watts, Anthony, "The Antiviral Peptide Carbobenzoxy-D-phenylalanyl-L-phenylalanylglycine Changes the Average Conformation of Phospholipids in Membranes" (1993). School of Dentistry Faculty Research and Publications. 256.
https://epublications.marquette.edu/dentistry_fac/256