Engineered Cationic Antimicrobial Peptides (eCAPs) manuscript titled “De Novo Generation of Cationic Antimicrobial Peptides: Influence of Length and Tryptophan Substitution on Antimicrobial Activity”
Engineered Cationic Antimicrobial Peptides was the first eCAP publication in AAC with the emerging lead eCAP WLBU2. the manuscript is attached.
These are the authors of the Engineered Cationic Antimicrobial Peptides (eCAPs) manuscript:
(1) Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, and (2) Department of Pediatrics, Children’s Hospital of Pittsburgh,2 Pittsburgh, Pennsylvania; *Corresponding author
Antimicrobial peptide, selective toxicity, multidrug-resistant bacteria, antimicrobial resistance, drug resistance, biofilm, antibiofilm acitivity, in vivo efficacy, broad-spectrum activity, broad spectrum, infection, antibiotic resistance, bacterial resistance, ESKAPE pathogens, Pseudomonas aeruginosa, Staphylococcus aureus, MSSA, MRSA
Comparison of human immunodeficiency virus lentiviral lytic peptide 1 with other host-derived peptides indicates that antimicrobial properties of membrane-active peptides are markedly influenced by their cationic, hydrophobic, and amphipathic properties. Many common themes, such as Arg composition of the cationic face of an amphipathic helix and the importance of maintaining the hydrophobic face, have been deduced from these observations. These studies suggest that a peptide with these structural properties can be derived de novo by using only a few strategically positioned amino acids. However, the effects of length and helicity on antimicrobial activity and selectivity have not been objectively evaluated in the context of this motif. To address these structure-function issues, multimers of a 12-residue lytic base unit (LBU) peptide composed only of Arg and Val residues aligned to form idealized amphipathic helices were designed. Bacterial killing assays and circular dichroism analyses reveal a strong correlation between antibacterial activity, peptide length, and propensity to form a helix in solvent mimicking the environment of a membrane. Increasing peptide length beyond two LBUs (24-residue peptides) resulted in no appreciable increase in antimicrobial activity. Derivatives (WLBU) of the LBU series were further engineered by substituting Trp residues in the hydrophobic domains. The 24-residue WLBU2 peptide was active at physiologic NaCl concentrations against Staphylococcus aureus and mucoid and nonmucoid strains of Pseudomonas aeruginosa. Further, WLBU2 displayed the highest antibacterial selectivity of all peptides evaluated in the present study by using a coculture model of P. aeruginosa and primary human skin fibroblasts. These findings provide fundamental information toward the de novo design of an antimicrobial peptide useful for the management of infectious diseases.
Here is a preview of the manuscript, which can also be downloaded using the pdf link below.
Engineered Cationic Antimicrobial Peptides, first eCAP publication in AAC with the emerging lead eCAP WLBU2. the manuscript is attached for download and can also be found on PUBMED.