, a bio/informatics shared resource is still "open for business" - Visit the CDS website

Helical antimicrobial polypeptides with radial amphiphilicity.

Xiong M, Lee MW, Mansbach RA, Song Z, Bao Y, Peek RM, Yao C, Chen LF, Ferguson AL, Wong GC, Cheng J
Proc Natl Acad Sci U S A. 2015 112 (43): 13155-60

PMID: 26460016 · PMCID: PMC4629321 · DOI:10.1073/pnas.1507893112

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.

MeSH Terms (4)

Antimicrobial Cationic Peptides Gram-Negative Bacteria Gram-Positive Bacteria Microbial Sensitivity Tests

Connections (1)

This publication is referenced by other Labnodes entities: