NMR studies of aurein 1.2 analogs

Xia Li, Yifeng Li, Alan Peterkofsky, Guangshun Wang

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Aurein 1.2 is an antimicrobial and anticancer peptide isolated from an Australian frog. To improve our understanding of the mechanism of action, two series of peptides were designed. The first series includes the N-terminal membrane anchor of bacterial glucose-specific enzyme IIA, aurein 1.2, and a newly identified aurein 1.2 analog from human LL-37 (LLAA). The order of antibacterial activity is LLAA > aurein 1.2 >> the membrane anchor (inactive). The structure of LLAA in detergent micelles was determined by 1H NMR spectroscopy, including structural refinement by natural abundance 13Cα, 13Cβ, and 15N chemical shifts. The hydrophobic surface area of the 3D structure is related to the retention time of the peptide on a reverse-phase HPLC column. The higher activity of LLAA compared to aurein 1.2 was attributed to additional cationic residues that enhance the membrane perturbation potential. The second peptide series was created by changing the C-terminal phenylalanine (F13) of aurein 1.2 to either phenylglycine or tryptophan. A closer or further location of the aromatic rings to the peptide backbone in the mutants relative to F13 is proposed to cause a drop in activity. Phenylglycine with unique chemical shifts may be a useful NMR probe for structure-activity relationship studies of antimicrobial peptides. To facilitate potential future use for NMR studies, random-coil chemical shifts for phenylglycine (X) were measured using the synthetic peptide GGXGG. Aromatic rings of phenylalanines in all the peptides penetrated 2-5 Å below the lipid head group and are essential for membrane targeting as illustrated by intermolecular peptide-lipid NOE patterns.

Original languageEnglish (US)
Pages (from-to)1203-1214
Number of pages12
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1758
Issue number9
DOIs
StatePublished - Sep 1 2006

Fingerprint

Nuclear magnetic resonance
Peptides
Chemical shift
Membranes
Anchors
Phenylalanine
Lipids
Micelles
Structure-Activity Relationship
Tryptophan
Anura
Detergents
Membrane Potentials
Nuclear magnetic resonance spectroscopy
Magnetic Resonance Spectroscopy
High Pressure Liquid Chromatography
Glucose
Enzymes

Keywords

  • Antimicrobial peptides
  • Aurein 1.2
  • LL-37
  • Peptide-lipid interaction
  • Phenylglycine
  • Random-coil chemical shifts

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

Cite this

NMR studies of aurein 1.2 analogs. / Li, Xia; Li, Yifeng; Peterkofsky, Alan; Wang, Guangshun.

In: Biochimica et Biophysica Acta - Biomembranes, Vol. 1758, No. 9, 01.09.2006, p. 1203-1214.

Research output: Contribution to journalArticle

Li, Xia ; Li, Yifeng ; Peterkofsky, Alan ; Wang, Guangshun. / NMR studies of aurein 1.2 analogs. In: Biochimica et Biophysica Acta - Biomembranes. 2006 ; Vol. 1758, No. 9. pp. 1203-1214.
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