A new series of small cationic lipidated peptidomimetics have been synthesized and found to be highly active against several susceptible as well as drug resistant clinical isolates of bacteria and fungi. All lipidated peptidomimetics do not cause significant lysis of human erythrocytes (HC50>200μg/mL). Calcein dye leakage experiment revealed membranolytic effect of LPEP08 which was further confirmed by scanning electron microscopy (SEM). The involvement of intracellular targets as an alternate mode of action was precluded by DNA retardation assay. Additionally, LPEP08 exhibit high proteolytic stability and dose not elicit resistance against drug resistant clinical isolate of Staphylococcusaureus, even after 16 rounds of passaging. These results demonstrate the potential of lipidated peptidomimetics as biocompatible anti-infective therapeutics.
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http://dx.doi.org/10.1016/j.bmc.2014.07.041 | DOI Listing |
ACS Appl Mater Interfaces
December 2024
School of Polymer Science and Polymer Engineering, The University of Akron, Akron, Ohio 44325, United States.
Modulating microbial motility and physiology can enhance the production of bacterial macromolecules and small molecules. Herein, a platform of water-soluble and amphiphilic peptidomimetic polyurethanes is reported as a means of regulating bacterial surface behavior and the concomitant production of extracellular polymeric substances (EPS). It is demonstrated that carboxyl (-COOH)-containing polyurethanes exhibited 17-fold and 80-fold enhancements in () swarming and twitching areas, respectively.
View Article and Find Full Text PDFACS Infect Dis
November 2024
Université Clermont Auvergne, Clermont Auvergne INP, CNRS, ICCF, F-63000 Clermont-Ferrand, France.
Bioinspired from cationic antimicrobial peptides, sequence-defined triazolium-grafted peptoid oligomers (6- to 12-mer) were designed to adopt an amphipathic helical polyproline I-type structure. Their evaluation on a panel of bacterial strains (, , , and ), pathogenic fungi (, , and ), and human cells (hRBC, BEAS-2B, Caco-2, HaCaT, and HepG2) enabled the identification of two heptamers with improved activity to selectively fight pathogens. Modulation of parameters such as the nature of the triazolium and hydrophobic/lipophilic side chains, the charge content, and the sequence length drastically potentiates activity and selectivity.
View Article and Find Full Text PDFJ Med Chem
September 2024
Department of Chemistry, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.
Antimicrobial peptides (AMPs) represent promising therapeutic modalities against multidrug-resistant bacterial infections. As a mimic of natural AMPs, peptidomimetic oligomers like peptoids (i.e.
View Article and Find Full Text PDFAdv Healthc Mater
October 2024
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, 511436, China.
The development of narrow-spectrum antimicrobial agents is paramount for swiftly eradicating pathogenic bacteria, mitigating the onset of drug resistance, and preserving the homeostasis of bacterial microbiota in tissues. Owing to the limited affinity between the hydrophobic lipid bilayer interior of bacterial cells and most hydrophilic, polar peptides, the construction of a distinctive class of four-armed host-defense peptides/peptidomimetics (HDPs) is proposed with enhanced specificity and membrane perturbation capability against Pseudomonas aeruginosa by incorporating imidazole groups. These groups demonstrate substantial affinity for unsaturated phospholipids, which are predominantly expressed in the cell membrane of P.
View Article and Find Full Text PDFFront Cardiovasc Med
June 2024
Department of Experimental Pathology, Institute of Biomedical Research of Barcelona (IIBB)-Spanish National Research Council (CSIC), Barcelona, Spain.
In recent years, the role of macrophages as the primary cell type contributing to foam cell formation and atheroma plaque development has been widely acknowledged. However, it has been long recognized that diffuse intimal thickening (DIM), which precedes the formation of early fatty streaks in humans, primarily consists of lipid-loaded smooth muscle cells (SMCs) and their secreted proteoglycans. Recent studies have further supported the notion that SMCs constitute the majority of foam cells in advanced atherosclerotic plaques.
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