Conformational Studies on Two FtsZ Targeting Cyclic Peptides

Two FtsZ targeting cyclic peptides 1 (Ac-[Orn-Leu-Met-Asp]-Ala-Phe-Arg-Ser-NH 2 ) and 2 (Ac-Ser-Leu-Met-[Asp-Ala-Phe-Arg-Orn]-NH 2 ) 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 investigat...

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Bibliographic Details
Published in:International journal of peptide research and therapeutics 2020-09, Vol.26 (3), p.1567-1573
Main Authors: Vidović, Nikolina, Recca, Teresa, Francescato, Pierangelo, Rabuffetti, Marco, Sironi, Maurizio, Oliva, Francesco, Pieraccini, Stefano, Speranza, Giovanna
Format: Article
Language:English
Subjects:
Animal Anatomy
Antimicrobial agents
Biochemistry
Biomedical and Life Sciences
Guanidine
Histology
Life Sciences
Molecular Medicine
Morphology
NMR
Nuclear magnetic resonance
Peptides
Pharmaceutical Sciences/Technology
Pharmacology/Toxicology
Polymer Sciences
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Summary:Two FtsZ targeting cyclic peptides 1 (Ac-[Orn-Leu-Met-Asp]-Ala-Phe-Arg-Ser-NH 2 ) and 2 (Ac-Ser-Leu-Met-[Asp-Ala-Phe-Arg-Orn]-NH 2 ) 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- d 6 , 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 .
ISSN:1573-3149
1573-3904
DOI:10.1007/s10989-019-09962-9