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Conformational Studies on Two FtsZ Targeting Cyclic Peptides

  • Nikolina VidovićEmail author
  • Teresa Recca
  • Pierangelo Francescato
  • Marco Rabuffetti
  • Maurizio Sironi
  • Francesco Oliva
  • Stefano Pieraccini
  • Giovanna SperanzaEmail author
Article
  • 16 Downloads

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.

Keywords

Cyclic peptides FtsZ targeting peptides Conformation NMR Molecular dynamics 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

This article does not contain any study with human or animals performed by any of the authors.

Supplementary material

10989_2019_9962_MOESM1_ESM.docx (1.3 mb)
Electronic supplementary material 1 (DOCX 1370 kb)

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of MilanMilanoItaly
  2. 2.Department of ChemistryUniversity of PaviaPaviaItaly
  3. 3.Department of Food, Environmental and Nutritional SciencesUniversity of MilanMilanoItaly
  4. 4.Institute of Molecular Science and Technologies (ISTM-CNR)MilanoItaly

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