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Synergy Between a Lead Proline-rich Antibacterial Peptide Derivative and Small Molecule Antibiotics

  • Laszlo Jr Otvos
  • Marco Cassone
  • Vanessa de Olivier Inacio
  • Paul Noto
  • John J. Rux
  • John D. Wade
  • Predrag Cudic
Part of the Advances in Experimental Medicine and Biology book series (volume 611)

Introduction

Proline-rich antimicrobial peptides kill bacteria by binding to the C-terminal D-E helix of DnaK, the 70 kDa bacterial heat shock protein and inhibiting chaperone-assisted protein folding [1]. Indeed, the strain selectivity of two family members, drosocin and pyrrhocoricin, and the D-E helix homology of Enterobactericeae can be fully correlated [2,3]. However, mechanistically it is still unclear how binding to the multihelical lid region would allosterically prevent substrate-DnaK interactions taking place 200 residues upstream. If a proper theoretical explanation can be found, the process can be utilized for the development of standalone peptide antibiotics, or for reversing resistance mechanisms that are developed against small molecule antibiotics where failure to kill microorganisms involves the activation of properly folded bacterial proteins, including enzymes. Newly introduced functional enzymes are responsible for the emerging resistance against once powerful...

Keywords

Haemophilus Influenzae Sublethal Dose Peptide Antibiotic Conventional Antibiotic Checkerboard Assay 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported by the Sbarro Health Research Organization.

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Laszlo Jr Otvos
    • 1
  • Marco Cassone
    • 1
  • Vanessa de Olivier Inacio
    • 2
  • Paul Noto
    • 1
  • John J. Rux
    • 3
  • John D. Wade
    • 4
  • Predrag Cudic
    • 2
  1. 1.Sbarro Institute for Cancer Research and Molecular MedicineTemple UniversityPhiladelphiaUSA
  2. 2.Department of Chemistry and BiochemistryFlorida Atlantic UniversityBoca RatonUSA
  3. 3.The Wistar InstitutePhiladelphiaPA
  4. 4.Howard Florey InstituteUniversity of MelbourneVictoriaAustralia

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