Conformational Studies on Two FtsZ Targeting Cyclic Peptides

Abstract

Two FtsZ targeting cyclic peptides 1 (Ac-[Orn-Leu-Met-Asp]-Ala-Phe-Arg-Ser-NH2) and 2 (Ac-Ser-Leu-Met-[Asp-Ala-Phe-Arg-Orn]-NH2) were found to be inhibitors of FtsZ polymerization, that makes them excellent starting point for the future development of a new class of antimicrobials. We investigated their solution structure by means of nuclear magnetic resonance (NMR) and molecular dynamic simulations (MD). Deep analysis of 2D NMR spectra (COSY, TOCSY and NOESY), recorded in DMSO-d6, allowed the assignments of all peptide signals and suggested the presence of strong turn structures. We also noticed that the guanidine group of Arg significantly affects the spectral properties and the chromatographic behavior of these peptides depending on whether it makes part of the cycle or not. MD simulations allowed to investigate the conformational preference of the two cyclic peptides and to associate diversity in their structure and dynamics to their different behavior. In particular, peptide 1 showed enhanced flexibility and structural variance with respect to peptide 2.

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Correspondence to Nikolina Vidović or Giovanna Speranza.

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Vidović, N., Recca, T., Francescato, P. et al. Conformational Studies on Two FtsZ Targeting Cyclic Peptides. Int J Pept Res Ther 26, 1567–1573 (2020). https://doi.org/10.1007/s10989-019-09962-9

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Keywords

  • Cyclic peptides
  • FtsZ targeting peptides
  • Conformation
  • NMR
  • Molecular dynamics