TY  - JOUR
A1  - Kuroki, Agnes
A1  - Tchoupa, Arnaud Kengmo
A1  - Hartlieb, Matthias
A1  - Peltier, Raoul
A1  - Locock, Katherine E. S.
A1  - Unnikrishnan, Meera
A1  - Perrier, Sebastien
T1  - Targeting intracellular, multi-drug resistant Staphylococcus aureus with guanidinium polymers by elucidating the structure-activity relationship
JF  - Biomaterials : biomaterials reviews online
N2  - Intracellular persistence of bacteria represents a clinical challenge as bacteria can thrive in an environment protected from antibiotics and immune responses. Novel targeting strategies are critical in tackling antibiotic resistant infections. Synthetic antimicrobial peptides (SAMPs) are interesting candidates as they exhibit a very high antimicrobial activity. We first compared the activity of a library of ammonium and guanidinium polymers with different sequences (statistical, tetrablock and diblock) synthesized by RAFT polymerization against methicillin-resistant S. aureus (MRSA) and methicillin-sensitive strains (MSSA). As the guanidinium SAMPs were the most potent, they were used to treat intracellular S. aureus in keratinocytes. The diblock structure was the most active, reducing the amount of intracellular MSSA and MRSA by two-fold. We present here a potential treatment for intracellular, multi-drug resistant bacteria, using a simple and scalable strategy.
KW  - Antimicrobial
KW  - Intracellular bacteria
KW  - Block copolymers
KW  - RAFT polymerization
Y1  - 2019
U6  - https://doi.org/10.1016/j.biomaterials.2019.119249
SN  - 0142-9612
SN  - 1878-5905
VL  - 217
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Hartlieb, Matthias
A1  - Catrouillet, Sylvain
A1  - Kuroki, Agnes
A1  - Sanchez-Cano, Carlos
A1  - Peltier, Raoul
A1  - Perrier, Sebastien
T1  - Stimuli-responsive membrane activity of cyclic-peptide-polymer conjugates
JF  - Chemical science
N2  - Cyclic peptide nanotubes (CPNT) consisting of an even number of amino acids with an alternating chirality are highly interesting materials in a biomedical context due to their ability to insert themselves into cellular membranes. However, unwanted unspecific interactions between CPNT and non-targeted cell membranes are a major drawback. To solve this issue we have synthetized a series of CPNT-polymer conjugates with a cleavable covalent connection between macromolecule and peptide. As a result, the polymers form a stabilizing and shielding shell around the nanotube that can be cleaved on demand to generate membrane active CPNT from non-active conjugates. This approach enables us to control the stacking and lateral aggregation of these materials, thus leading to stimuli responsive membrane activity. Moreover, upon activation, the systems can be adjusted to form nanotubes with an increased length instead of aggregates. We were able to study the dynamics of these systems in detail and prove the concept of stimuli responsive membrane interaction using CPNT-polymer conjugates to permeabilize liposomes as well as mammalian cell membranes.
Y1  - 2019
U6  - https://doi.org/10.1039/c9sc00756c
SN  - 2041-6520
SN  - 2041-6539
VL  - 10
IS  - 21
SP  - 5476
EP  - 5483
PB  - Royal Society of Chemistry
CY  - Cambridge
ER  -