Elucidation of the structure of constrained bicyclopeptides in solution by two-dimensional cross-relaxation spectroscopy: Amatoxin analogues

Carla Isernia, Lucia Falcigno, Slobodan Macura, Livio Paolillo, Anna Lisa Pastore, Giancarlo Zanotti

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The evaluation of peptide structures in solution is made feasible by the combined use of two-dimensional NMR in the laboratory (NOESY) and rotating frames (ROESY), and by the use of molecular dynamics calculations. The present paper describes how both the NMR method and molecular dynamics calculations were applied to very rigid synthetic bicyclic peptides that are analogues of natural amatoxins. The NMR theory, which allows the estimate of interatomic distances between interacting nuclei, is briefly discussed. The experimental data were compared with those of known solid-state structures. Three amatoxin analogues have been examined. Of these, one is biologically active (S-deoxo γ[R] OH-Ile3-amaninamide) and its structure in the solid state has recently been worked out. The second and third analogues (S-deoxo-Ile3-Ala5-amaninamide and S-deoxo-D-Ile3-amaninamide, respectively) are inactive and their solid-state structures are unknown. The data presented confirm the authors' previous hypothesis that lack of biological activity of S-deoxo-Ile3-Ala5-amaninamide is due to the masking of the tryptophan ring by the methyl group of L-Ala and not to massive conformational changes of the analogue.

Original languageEnglish (US)
Pages (from-to)3-13
Number of pages11
JournalJournal of Peptide Science
Volume2
Issue number1
DOIs
StatePublished - Jan 1 1996

Keywords

  • Constrained bicyclopeptides
  • Molecular dynamics
  • NMR
  • Structure of amatoxin analogues

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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