A miniature mimic of host defense peptides with systemic antibacterial efficacy.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Hadar SarigAmram Mor

Abstract

Oligomers of acylated lysines (OAKs) are synthetic mimics of host defense peptides (HDPs) with promising antimicrobial properties. Here we challenged the OAK concept for its ability to generate both systemically efficient and economically viable lead compounds for fighting multidrug-resistant bacteria. We describe the design and characterization of a miniature OAK composed of only 3 lysyls and 2 acyls (designated C(12(omega7))K-beta(12)) that preferentially targets gram-positive species by a bacteriostatic mode of action. To gain insight into the mechanism of action, we examined the interaction of OAK with various potential targets, including phospholipid bilayers, using surface plasmon resonance, and Langmuir monolayers, using insertion assays, epifluorescence microscopy, and grazing incidence X-ray diffraction, in a complementary manner. Collectively, the data support the notion that C(12(omega7))K-beta(12) damages the plasma-membrane architecture similarly to HDPs, that is, following a near-classic 2-step interaction including high-affinity electrostatic adhesion and a subsequent shallow insertion that was limited to the phospholipid head group region. Notably, preliminary acute toxicity and efficacy studies performed with m...Continue Reading

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Citations

Aug 22, 2013·Journal of Medicinal Chemistry·Ianire MartinArturo Muga
Jun 8, 2011·Antimicrobial Agents and Chemotherapy·Fadia ZaknoonAmram Mor
Jul 4, 2012·Antimicrobial Agents and Chemotherapy·Fadia ZaknoonAmram Mor
Apr 14, 2010·Antimicrobial Agents and Chemotherapy·Yair GoldfederAmram Mor
Nov 16, 2011·Antimicrobial Agents and Chemotherapy·Guangshun WangRichard M Epand
Apr 12, 2012·Antimicrobial Agents and Chemotherapy·Sheng-An LiYun Zhang
May 21, 2011·Cellular and Molecular Life Sciences : CMLS·Andrea Giuliani, Andrea C Rinaldi
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Jun 1, 2014·Biochimica Et Biophysica Acta·Konstantin AndreevDavid Gidalevitz
Mar 19, 2015·Scientific Reports·Joanna JammalAmram Mor
Nov 3, 2015·Biochimica Et Biophysica Acta·Galoz KanetiAmram Mor
Aug 5, 2017·Journal of Biomedical Materials Research. Part a·Maja Kaisersberger VincekVanja Kokol
Aug 24, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Galoz KanetiAmram Mor
Jun 5, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Keren GoldbergAmram Mor
Aug 20, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·L LivneA Mor
May 21, 2017·Scientific Reports·Ohad MeirAmram Mor
Sep 1, 2017·Antonie van Leeuwenhoek·Xiaojing XiaJianhe Hu
Feb 17, 2017·Frontiers in Microbiology·Katarzyna E GreberWieslaw Sawicki

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