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Title: Cyclization improves membrane permeation by antimicrobial peptoids

The peptidomimetic approach has emerged as a powerful tool for overcoming the inherent limitations of natural antimicrobial peptides, where the therapeutic potential can be improved by increasing the selectivity and bioavailability. Restraining the conformational flexibility of a molecule may reduce the entropy loss upon its binding to the membrane. Experimental findings demonstrate that the cyclization of linear antimicrobial peptoids increases their bactericidal activity against Staphylococcus aureus while maintaining high hemolytic concentrations. Surface X-ray scattering shows that macrocyclic peptoids intercalate into Langmuir monolayers of anionic lipids with greater efficacy than for their linear analogues. Lastly, it is suggested that cyclization may increase peptoid activity by allowing the macrocycle to better penetrate the bacterial cell membrane.
Authors:
 [1] ;  [2] ;  [1] ;  [3] ;  [4] ;  [5] ;  [5] ;  [3] ;  [1]
  1. Illinois Institute of Technology, Chicago, IL (United States)
  2. Illinois Institute of Technology, Chicago, IL (United States); Argonne National Lab. (ANL), Lemont, IL (United States)
  3. New York Univ. (NYU), New York, NY (United States)
  4. Argonne National Lab. (ANL), Lemont, IL (United States)
  5. Univ. of Chicago, Chicago, IL (United States)
Publication Date:
Grant/Contract Number:
AC02-06CH11357
Type:
Accepted Manuscript
Journal Name:
Langmuir
Additional Journal Information:
Journal Volume: 32; Journal Issue: 48; Journal ID: ISSN 0743-7463
Publisher:
American Chemical Society
Research Org:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org:
National Science Foundation (NSF); National Institutes of Health (NIH); USDOE Office of Science (SC)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
OSTI Identifier:
1343314

Andreev, Konstantin, Martynowycz, Michael W., Ivankin, Andrey, Huang, Mia L., Kuzmenko, Ivan, Meron, Mati, Lin, Binhua, Kirshenbaum, Kent, and Gidalevitz, David. Cyclization improves membrane permeation by antimicrobial peptoids. United States: N. p., Web. doi:10.1021/acs.langmuir.6b03477.
Andreev, Konstantin, Martynowycz, Michael W., Ivankin, Andrey, Huang, Mia L., Kuzmenko, Ivan, Meron, Mati, Lin, Binhua, Kirshenbaum, Kent, & Gidalevitz, David. Cyclization improves membrane permeation by antimicrobial peptoids. United States. doi:10.1021/acs.langmuir.6b03477.
Andreev, Konstantin, Martynowycz, Michael W., Ivankin, Andrey, Huang, Mia L., Kuzmenko, Ivan, Meron, Mati, Lin, Binhua, Kirshenbaum, Kent, and Gidalevitz, David. 2016. "Cyclization improves membrane permeation by antimicrobial peptoids". United States. doi:10.1021/acs.langmuir.6b03477. https://www.osti.gov/servlets/purl/1343314.
@article{osti_1343314,
title = {Cyclization improves membrane permeation by antimicrobial peptoids},
author = {Andreev, Konstantin and Martynowycz, Michael W. and Ivankin, Andrey and Huang, Mia L. and Kuzmenko, Ivan and Meron, Mati and Lin, Binhua and Kirshenbaum, Kent and Gidalevitz, David},
abstractNote = {The peptidomimetic approach has emerged as a powerful tool for overcoming the inherent limitations of natural antimicrobial peptides, where the therapeutic potential can be improved by increasing the selectivity and bioavailability. Restraining the conformational flexibility of a molecule may reduce the entropy loss upon its binding to the membrane. Experimental findings demonstrate that the cyclization of linear antimicrobial peptoids increases their bactericidal activity against Staphylococcus aureus while maintaining high hemolytic concentrations. Surface X-ray scattering shows that macrocyclic peptoids intercalate into Langmuir monolayers of anionic lipids with greater efficacy than for their linear analogues. Lastly, it is suggested that cyclization may increase peptoid activity by allowing the macrocycle to better penetrate the bacterial cell membrane.},
doi = {10.1021/acs.langmuir.6b03477},
journal = {Langmuir},
number = 48,
volume = 32,
place = {United States},
year = {2016},
month = {10}
}