title: Arginine-rich self-assembling peptides as potent antibacterial gels.
abstract: Hydrogel materials that display inherent activity against bacteria can be used to directly treat accessible wounds to prevent or kill existing infection. Hydrogels composed of self-assembling β-hairpin peptides, having a high content of arginine, were found to be extremely effective at killing both gram-positive and gram-negative bacteria, including multi-drug resistant Pseudomonas aeruginosa. No added antibacterial agents are necessary to realize activity. Using self-assembling peptides for material construction allows facile structure-activity relationships to be determined since changes in peptide sequence at the monomer level are directly transposed to the bulk material's antibacterial properties. SAR studies show that arginine content largely influences the hydrogel's antibacterial activity, and influences their bulk rheological properties. These studies culminated in an optimized gel, composed of the peptide PEP6R (VKVRVRVRV(D)PPTRVRVRVKV). PEP6R gels prepared at 1.5 wt % or higher concentration, demonstrate high potency against bacteria, but are cytocompatible toward human erythrocytes as well as mammalian mesenchymal stem cells. Rheological studies indicate that the gel is moderately stiff and displays shear-thin recovery behavior, allowing its delivery via simple syringe.
authors.affiliation: Chemical Biology Lab, National Cancer Institute, Frederick, MD 21702, USA.
authors.forename: Ana Salomé
authors.initials: AS
authors.lastname: Veiga
authors.forename: Chomdao
authors.initials: C
authors.lastname: Sinthuvanich
authors.forename: Diana
authors.initials: D
authors.lastname: Gaspar
authors.forename: Henri G
authors.initials: HG
authors.lastname: Franquelim
authors.forename: Miguel A R B
authors.initials: MA
authors.lastname: Castanho
authors.forename: Joel P
authors.initials: JP
authors.lastname: Schneider
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001120:Arginine / Q000737:chemistry / Q000494:pharmacology*; D002942:Circular Dichroism; D024901:Drug Resistance, Multiple, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D019791:Guanidine / Q000737:chemistry / Q000494:pharmacology; D053878:Hemolytic Agents / Q000494:pharmacology; D020100:Hydrogels / Q000737:chemistry; D008239:Lysine / Q000737:chemistry; D050296:Microbial Viability; D018625:Microscopy, Atomic Force; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D053878:Hemolytic Agents; D020100:Hydrogels; D010455:Peptides; D001120:Arginine; D019791:Guanidine; D008239:Lysine