Development of Next Generation Antimicrobial Peptides as Antimicrobial Therapy
Technical Report,21 Sep 2017,20 Mar 2019
Singapore Institute of Technology Dover Singapore
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The PI and team were successful in this research project. Briefly, the first aim of this project is to develop synthetic AMPs with good bactericidal properties, coupled with excellent biocompatibility, for potential in vitro andor clinical translation. The second aim of this project is to develop a biological platform to cost effectively produce AMPs at reasonable scale. Using a parent peptide that showed promising broad spectrum antimicrobial characteristics, rational engineering was performed to enhance cationicity, hydrophobic-to-charge ratio and amphipathicity of the peptide analogues. One of the peptide analogues, 23R, stood out as a promising candidate, demonstrating broad spectrum antimicrobial characteristics, with low minimum bactericidal concentration MBC values against most gram-positive and gram-negative bacteria. The adoption of an alpha-helical conformation when exposed to microbial membrane appears to be important to disrupt phospholipid arrangement and eventual disintegration of bacteria membrane. The rapid membrane targeting mode of action also minimizes the possibility of resistance development by the microbes. Safety and efficacy studies of 23R in an animal wounding model demonstrated that the candidate peptide is able to perform under the dynamic physiological condition, significantly inhibiting microbial manifestation at the wound site. This peptide is expected to have broad applicability in antimicrobial protection. A peer reviewed manuscript is in preparation and a conference presentation is in preparation as well as a direct result of the grant funding. There were 1 research assistant and a student supported under this grant.
- Medicine and Medical Research