Oral Presentation 5th Modern Solid Phase Peptide Synthesis Symposium 2015

Potent proline-rich antimicrobial peptides against nosocomial Gram-negative bacteria (#24)

Li Wenyi 1 2 , Julien Tailhades 2 , Akhter Hossain 1 2 , Neil O’Brien-Simpson 3 4 , Eric Reynolds 3 4 , Laszlo Otvos 5 , Frances Separovic 1 3 , John Wade 1 2
  1. School of Chemistry, University of Melbourne, Parkville, VIC, Australia
  2. The Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia
  3. Bio21 Institute, University of Melbourne, Melbourne, VIC, Australia
  4. Oral Health CRC, Melbourne Dental School, University of Melbourne, Melbourne, VIC, Australia
  5. Department of Biology, Temple University, Philadelphia, PA, USA

Due to their broad-spectrum activity and distinct modes of action, antimicrobial peptides (AMPs) are considered as potential alternatives to combat the widespread adapting resistance of pathogens to conventional antibiotics1. Among them, the proline-rich AMPs (PrAMPs) family has been extensively studied as potential agents for a new generation of antibiotics2.

Previously, we showed by high resolution microscopy and flow cytometry that the alteration of mechanism of antibacterial action of a designed proline-rich antimicrobial peptide (PrAMP), Chex1-Arg20, with increasing valency from monomer to dimer and tetramer3. Furthermore, the effects of a series of N- and C-terminal modifications of the monomeric PrAMP, Chex1-Arg20, were studied on a panel of Gram-negative bacteria4. It was shown that C-terminal modifications with hydrazide or alcohol functions significantly extended their antibacterial activity against A. baumannii and P. aeruginosa. Thus, these engineered PrAMPs, modified Chex1-Arg20 and tetrameric highlight the value of solid phase synthesis to advance the development of novel compounds with strong activity against nosocomial Gram-negative bacteria (E. coli, K. pneumonia, A. baumannii and P.aeruginosa).

  1. L. Otvos, Jr., J. D. Wade, F. Lin, B. A. Condie, J. Hanrieder and R. Hoffmann, J. Med. Chem., 2005, 48, 5349-5359.
  2. W. Li, J. Tailhades, N. O’Brien-Simpson, F. Separovic, L. Otvos, Jr., M. A. Hossain and J. Wade, Amino Acids, 2014, 46, 2287-2294.
  3. W. Li, N. O'Brien-Simpson, J. Tailhades, N. Pantarat, R. Dawson, E. Reynolds, F. Separovic, M. Hossain and J. Wade, (submitted), 2015.
  4. W. Li, J. Tailhades, M. A. Hossain, N. M. O’Brien-Simpson, E. C. Reynolds, L. Otvos, F. Separovic and J. D. Wade, Aust. J. Chem., 2015, in press.