title: Helical antimicrobial polypeptides with radial amphiphilicity.
abstract: α-Helical antimicrobial peptides (AMPs) generally have facially amphiphilic structures that may lead to undesired peptide interactions with blood proteins and self-aggregation due to exposed hydrophobic surfaces. Here we report the design of a class of cationic, helical homo-polypeptide antimicrobials with a hydrophobic internal helical core and a charged exterior shell, possessing unprecedented radial amphiphilicity. The radially amphiphilic structure enables the polypeptide to bind effectively to the negatively charged bacterial surface and exhibit high antimicrobial activity against both gram-positive and gram-negative bacteria. Moreover, the shielding of the hydrophobic core by the charged exterior shell decreases nonspecific interactions with eukaryotic cells, as evidenced by low hemolytic activity, and protects the polypeptide backbone from proteolytic degradation. The radially amphiphilic polypeptides can also be used as effective adjuvants, allowing improved permeation of commercial antibiotics in bacteria and enhanced antimicrobial activity by one to two orders of magnitude. Designing AMPs bearing this unprecedented, unique radially amphiphilic structure represents an alternative direction of AMP development; radially amphiphilic polypeptides may become a general platform for developing AMPs to treat drug-resistant bacteria.
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801;
authors.forename: Menghua
authors.initials: M
authors.lastname: Xiong
authors.affiliation: Department of Bioengineering, Department of Chemistry and Biochemistry, California NanoSystems Institute, University of California, Los Angeles, CA 90095;
authors.forename: Michelle W
authors.identifier: http://orcid.org/0000-0003-1613-9501
authors.initials: MW
authors.lastname: Lee
authors.affiliation: Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL 61801;
authors.forename: Rachael A
authors.initials: RA
authors.lastname: Mansbach
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801;
authors.forename: Ziyuan
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801;
authors.forename: Yan
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Division of Gastroenterology, Department of Medicine and Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232;
authors.forename: Richard M
authors.initials: RM
authors.lastname: Peek
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801;
authors.forename: Catherine
authors.initials: C
authors.lastname: Yao
authors.affiliation: Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801;
authors.forename: Lin-Feng
authors.initials: LF
authors.lastname: Chen
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801; Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801 alf@illinois.edu gclwong@seas.ucla.edu jianjunc@illinois.edu.
authors.forename: Andrew L
authors.identifier: http://orcid.org/0000-0002-8829-9726
authors.initials: AL
authors.lastname: Ferguson
authors.affiliation: Department of Bioengineering, Department of Chemistry and Biochemistry, California NanoSystems Institute, University of California, Los Angeles, CA 90095; alf@illinois.edu gclwong@seas.ucla.edu jianjunc@illinois.edu.
authors.forename: Gerard C L
authors.initials: GC
authors.lastname: Wong
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801; alf@illinois.edu gclwong@seas.ucla.edu jianjunc@illinois.edu.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Cheng
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests
chemical_list: D023181:Antimicrobial Cationic Peptides
keywords: antimicrobial peptide; bacteria; polypeptides; radial amphiphilicity; α-helix