Comparative Properties of Helical and Linear Amphipathicity of Peptides Composed of Arginine, Tryptophan, and Valine.

Antibiotics (Basel)

Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Published: October 2024

Background: The persistence of antibiotic resistance has incited a strong interest in the discovery of agents with novel antimicrobial mechanisms. The direct killing of multidrug-resistant bacteria by cationic antimicrobial peptides (AMPs) underscores their importance in the fight against infections associated with antibiotic resistance. Despite a vast body of AMP literature demonstrating a plurality in structural classes, AMP engineering has been largely skewed toward peptides with idealized amphipathic helices (H-amphipathic). In contrast to helical amphipathicity, we designed a series of peptides that display the amphipathic motifs in the primary structure. We previously developed a rational framework for designing AMP libraries of H-amphipathic peptides consisting of Arg, Trp, and Val (H-RWV, with a confirmed helicity up to 88% in the presence of membrane lipids) tested against the most common MDR organisms.

Methods: In this study, we re-engineered one of the series of the H-RWV peptides (8, 10, 12, 14, and 16 residues in length) to display the amphipathicity in the primary structure by side-by-side (linear) alignment of the cationic and hydrophobic residues into the 2 separate linear amphipathic (L-amphipathic) motifs. We compared the 2 series of peptides for antibacterial activity, red blood cell (RBC) lysis, killing and membrane-perturbation properties.

Results: The L-RWV peptides achieved the highest antibacterial activity at a minimum length of 12 residues (L-RWV12, minimum optimal length or MOL) with the lowest mean MIC of 3-4 µM, whereas the MOL for the H-RWV series was reached at 16 residues (H-RWV16). Overall, H-RWV16 displayed the lowest mean MIC at 2 µM but higher levels of RBC lysis (25-30%), while the L-RWV series displayed minor RBC lytic effects at the test concentrations. Interestingly, when the strain SA719 was chosen because of its susceptibility to most of the peptides, none of the L-RWV peptides demonstrated a high level of membrane perturbation determined by propidium iodide incorporation measured by flow cytometry, with <50% PI incorporation for the L-RWV peptides. By contrast, most H-RWV peptides displayed almost up to 100% PI incorporation. The results suggest that membrane perturbation is not the primary killing mechanism of the L-amphipathic RWV peptides, in contrast to the H-RWV peptides.

Conclusions: Taken together, the data indicate that both types of amphipathicity may provide different ideal pharmacological properties that deserve further investigation.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504230PMC
http://dx.doi.org/10.3390/antibiotics13100954DOI Listing

Publication Analysis

Top Keywords

peptides
10
antibiotic resistance
8
series peptides
8
primary structure
8
antibacterial activity
8
rbc lysis
8
l-rwv peptides
8
lowest mic
8
series
5
comparative properties
4

Similar Publications

Retraction notice to "Scorpion peptide LqhIT2 activates phenylpropanoid pathways via jasmonate to increase rice resistance to rice leafrollers" [Plant Sci. 230 (2015) 1-11].

Plant Sci

January 2025

State Key Laboratory of Hybrid Rice, Key Laboratory for Research and Utilization of Heterosis in Indica Rice of the Ministry of Agriculture, Engineering Research Center for Plant Biotechology and Germplasm Utilization of the Ministry of Education, College of Life Science, Wuhan University, Wuhan 430072, China.

View Article and Find Full Text PDF

RosettaHDX: Predicting antibody-antigen interaction from hydrogen-deuterium exchange mass spectrometry data.

J Struct Biol

January 2025

Center of Structural Biology, Vanderbilt University, Nashville, TN, USA; Department of Chemistry, Vanderbilt University, Nashville, TN, USA; Institute for Drug Discovery, Institute for Computer Science, Wilhelm Ostwald Institute for Physical and Theoretical Chemistry, University Leipzig, Leipzig, Germany; Center for Scalable Data Analytics and Artificial Intelligence ScaDS.AI and School of Embedded Composite Artificial Intelligence SECAI, Dresden/Leipzig, Germany; Department of Pharmacology, Institute of Chemical Biology, Center for Applied Artificial Intelligence in Protein Dynamics, Vanderbilt University, Nashville, TN, USA. Electronic address:

High-throughput characterization of antibody-antigen complexes at the atomic level is critical for understanding antibody function enabling therapeutic development. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) enables rapid epitope mapping, but its data are too sparse for independent structure determination. In this study, we introduce RosettaHDX, a hybrid method that combines computational docking with differential HDX-MS data to enhance the accuracy of antibody-antigen complex models beyond what either method can achieve individually.

View Article and Find Full Text PDF

The benefits of Lactiplantibacillus plantarum: from immunomodulator to vaccine vector.

Immunol Lett

January 2025

Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria. Electronic address:

Probiotics have been increasingly recognized for positively influencing many aspects of human health. Lactiplantibacillus plantarum (L. plantarum), a non-pathogenic bacterium, previously known as Lactobacillus plantarum, is one of the lactic acid bacteria commonly used in fermentation.

View Article and Find Full Text PDF

Weight gain among persons with HIV PWH) on contemporary antiretroviral therapy (ART) can extend beyond an initial return-to-health phenomenon and lead to overweight/obesity in the first 1 to 2 years, resulting in enhanced cardiometabolic risk. Factors that may contribute to increased weight gain include specific ART regimens (those initiating dolutegravir and tenofovir alafenamide or withdrawing tenofovir disoproxil and efavirenz), women with HIV, and certain virologic factors including lower baseline CD4 count and higher HIV viral load. Weight reduction starting at 5% body weight confers metabolic protection, such as improved hypertension and dysglycemia.

View Article and Find Full Text PDF

Multiple mechanisms of action for an extremely painful venom.

Curr Biol

December 2024

Department of Biology, Indiana University, Bloomington, IN 47405, USA; Gill Institute for Neuroscience, Indiana University, Bloomington, IN 47405, USA; Program in Neuroscience, Indiana University, Bloomington, IN 47405, USA. Electronic address:

Evolutionary arms races can lead to extremely specific and effective defense mechanisms, including venoms that deter predators by targeting nociceptive (pain-sensing) pathways. The venom of velvet ants (Hymenoptera: Mutillidae) is notoriously painful. It has been described as "Explosive and long lasting, you sound insane as you scream.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!