TY - JOUR
T1 - Antimicrobial PEGtides
T2 - A Modular Poly(ethylene glycol)-Based Peptidomimetic Approach to Combat Bacteria
AU - Kim, Minseong
AU - Mun, Wonsik
AU - Jung, Woo Hyuk
AU - Lee, Joonhee
AU - Cho, Gayoung
AU - Kwon, Jisoo
AU - Ahn, Dong June
AU - Mitchell, Robert J.
AU - Kim, Byeong Su
N1 - Funding Information:
This work was primarily supported by Samsung Research Funding & Incubation Center of Samsung Electronics under Project Number SRFC-MA1602-07. This work was also supported by the National Research Foundation of Korea (NRF-2021R1A2C3004978, NRF-2020R1A2C2012158, and NRF-2021R1A2C3009955).
Publisher Copyright:
© 2021 American Chemical Society.
PY - 2021/5/25
Y1 - 2021/5/25
N2 - Despite their high potency, the widespread implementation of natural antimicrobial peptides is still challenging due to their low scalability and high hemolytic activities. Herein, we address these issues by employing a modular approach to mimic the key amino acid residues present in antimicrobial peptides, such as lysine, leucine, and serine, but on the highly biocompatible poly(ethylene glycol) (PEG) backbone. A series of these PEG-based peptides (PEGtides) were developed using functional epoxide monomers, corresponding to each key amino acid, with several possessing highly potent bactericidal activities and controlled selectivities, with respect to their hemolytic behavior. The critical role of the composition and the structure of the PEGtides in their selectivities was further supported by coarse-grained molecular dynamic simulations. This modular approach is anticipated to provide the design principles necessary for the future development of antimicrobial polymers.
AB - Despite their high potency, the widespread implementation of natural antimicrobial peptides is still challenging due to their low scalability and high hemolytic activities. Herein, we address these issues by employing a modular approach to mimic the key amino acid residues present in antimicrobial peptides, such as lysine, leucine, and serine, but on the highly biocompatible poly(ethylene glycol) (PEG) backbone. A series of these PEG-based peptides (PEGtides) were developed using functional epoxide monomers, corresponding to each key amino acid, with several possessing highly potent bactericidal activities and controlled selectivities, with respect to their hemolytic behavior. The critical role of the composition and the structure of the PEGtides in their selectivities was further supported by coarse-grained molecular dynamic simulations. This modular approach is anticipated to provide the design principles necessary for the future development of antimicrobial polymers.
KW - functional epoxide monomer
KW - molecular dynamic simulation
KW - peptidomimetics
KW - polyethers
KW - polymeric antimicrobials
UR - http://www.scopus.com/inward/record.url?scp=85106358461&partnerID=8YFLogxK
U2 - 10.1021/acsnano.1c02644
DO - 10.1021/acsnano.1c02644
M3 - Article
C2 - 33988968
AN - SCOPUS:85106358461
VL - 15
SP - 9143
EP - 9153
JO - ACS Nano
JF - ACS Nano
SN - 1936-0851
IS - 5
ER -