Helical antimicrobial polypeptides with radial amphiphilicity
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 antimicrobia...
Saved in:
Published in: | Proceedings of the National Academy of Sciences - PNAS Vol. 112; no. 43; pp. 13155 - 13160 |
---|---|
Main Authors: | , , , , , , , , , , |
Format: | Journal Article |
Language: | English |
Published: |
United States
National Academy of Sciences
27-10-2015
National Acad Sciences |
Subjects: | |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | 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. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 1M.X. and M.W.L. contributed equally to this work. Author contributions: M.X., M.W.L., G.C.L.W., and J.C. designed research; M.X., M.W.L., R.A.M., Z.S., Y.B., and A.L.F. performed research; M.X., M.W.L., R.M.P., L.-F.C., A.L.F., G.C.L.W., and J.C. analyzed data; and M.X., M.W.L., C.Y., A.L.F., G.C.L.W., and J.C. wrote the paper. Edited by Alexander M. Klibanov, Massachusetts Institute of Technology, Cambridge, MA, and approved September 18, 2015 (received for review April 23, 2015) |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.1507893112 |