Self-aggregation properties of spin-labeled zervamicin IIA as studied by PELDOR spectroscopy.
In this article, the pulsed double electron-electron resonance in electron spin-echo (PELDOR) technique is applied to study the self-aggregation of spin-labeled zervamicin IIA, a hexadecapeptide antibiotic of fungal origin, which is known to form ion channels in a phospholipid double layer. Measurements of the ion channel forming properties and the antibiotic activity of the analog indicate that replacement of the C-terminal phenylalaninol by the amino-2,2,6,6-tetramethylpiperidinyloxy (TEMPO) residue does not influence the biophysical and biological properties. The dipole-dipole interaction between the spin labels of the fully biologically active peptide analog was studied in frozen (77 K) glassy solutions in different ratios of toluene-methanol. The spin-labeled zervamicin IIA molecules were shown to form aggregates. An average distance between the spin labels in the aggregates was estimated to be in the range of 25-35 A (depending on the solvent composition), indicating that the amphiphilic helical peptide molecules are oriented in an antiparallel fashion. Increasing of methanol content in the solution results in a loosening of the aggregate structure. It was shown that the fraction of aggregated zervamicin IIA molecules is less than 44-67% depending on the solvent composition. The general usefulness of the method to obtain structural long-range information in a range of several tens of angstroms is demonstrated by comparison with the peptide cluster of trichogin GA IV.
Milov
A D
AD
Institute of Chemical Kinetics and Combustion, Russian Academy of Sciences, 630090 Novosibirsk, Russian Federation.
Tsvetkov
Yu D
YD
Gorbunova
E Yu
EY
Mustaeva
L G
LG
Ovchinnikova
T V
TV
Raap
J
J
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D000432:Methanol; D054848:Peptaibols; D010455:Peptides; D013113:Spin Labels; D014050:Toluene
D000900:Anti-Bacterial Agents; D054848:Peptaibols; D010455:Peptides; D013113:Spin Labels; D014050:Toluene; C051145:zervamicin IIA; D000432:Methanol