Self‐aggregation properties of spin‐labeled zervamicin IIA as studied by PELDOR spectroscopy

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Abstract
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 Å (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. © 2002 Wiley Periodicals, Inc. Biopolymers 64: 328–336, 2002