Cyclization of Two Antimicrobial Peptides Improves Their Activity
Year: 2025
Type: article
Abstract: One promising strategy to combat worldwide antimicrobial resistance involves using cyclic peptides as antibacterial agents. Cyclization of peptides can confer several advantages, including enhanced stability to proteolysis, decreased toxicity and increased bactericidal efficacy. This paper examines two cyclic peptides CE-03 (12 AAs) and CE-05 (16 AAs) and evaluates their effectiveness in combating bacterial infections, their stability and toxicity. We compare them to their linear versions. Circular dichroism (CD) reveals that CE-03 and CE-05 both adopt random coil and β-sheet structures in lipid model membranes (LMMs) mimicking G(-) and G(+) bacteria, where they are both bactericidal. Using X-ray diffuse scattering (XDS), their effects on lipid model membranes show a deep penetration of both peptides into eukaryotic LMMs where they are nontoxic, while a headgroup location in bacterial LMMs correlates with bacterial killing. Neutron reflectometry (NR) confirms the AMP locations determined using XDS. Further, solution small-angle X-ray scattering demonstrates that both peptides induce vesicle fusion in bacterial LMMs without affecting eukaryotic LMMs. Proteolytic degradation studies show that both CE-05 and CE-03 do not lose activity when incubated with the elastase enzyme, while the helical E2-35 AMP becomes inactive upon proteolysis.
Source: ACS Omega
Authors: Saheli Mitra, Mei-Tung Chen, Francisca Stedman, Jedidiah Hernandez, Grace Kumble, Xi Kang, Churan Zhang, Grace Tang, Iris Reed, Ian Q. Daugherty, Wanqing Liu, Kevin Raphael Klucznik, Jeremy L. Ocloo, Alexander Anzhi Li, Jessie Klousnitzer, Frank Heinrich, Berthony Deslouches, Stephanie Tristram-Nagle
Language: English
Subfield: Microbiology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,935
Funders: National Institute of Standards and Technology, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, Division of Materials Research, Division of Molecular and Cellular Biosciences, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases
Awards: G3299357311, G4921100856, G4965881104, G5078591404, COMPREHENSIVE CENTER-OF-EXCELLENCE INITIATIVE FOR BIOLOGICAL METROLOGY, G7051197921, PURPOSE: THE PURPOSE OF THIS GRANT IS TO ADVANCE NEUTRON-BASED MEASUREMENTS TO SUPPORT KEY INDUSTRIES OF THE US ECONOMY. TO SUPPORT THE PROPOSED COLLABORATION TO MEET EXISTING AND EMERGING NEEDS OF STAKEHOLDERS IN BIOTECHNOLOGY AND BIOMANUFACTURING.ACTIVITIES TO BE PERFORMED: DEVELOPMENT IN SAMPLE PREPARATION AND ANALYSIS, AS WELL AS CUTTING-EDGE AND VITAL FUNDAMENTAL RESEARCH PROBLEMS THAT MUST BE ADDRESSED IN BIOTECHNOLOGY AND BIOMANUFACTURING. THIS WILL IMPACT NOVICE USERS OF NEUTRON SCATTERING WHILE AT THE SAME TIME CREATING INNOVATIVE MEASUREMENT AND ANALYSIS MODALITIES FOR FUTURE APPLICATIONS. EXPAND THE RESEARCH PROGRAMS IN NEUTRONS AND, SEPARATELY, ARTIFICIAL INTELLIGENCE AND PROVIDE NEW EDUCATIONAL OPPORTUNITIES TO UNDERGRADUATE, GRADUATE, AND POST-GRADUATE STUDENTS OF CARNEGIE MELLON.EXPECTED OUTCOMES: INNOVATIONS IN SAMPLE PREPARATION AND ANALYSIS, AS WELL AS CUTTING-EDGE AND VITAL FUNDAMENTAL RESEARCH PROBLEMS. THIS WILL IMPACT NOVICE USERS OF NEUTRON SCATTERING WHILE AT THE SAME TIME CREATING INNOVATIVE MEASUREMENT AND ANALYSIS MODALITIES FOR FUTURE APPLICATIONS.INTENDED BENEFICIARIES: CARNEGIE MELLON UNIVERSITY WILL BENEFIT BY ADVANCED SCIENTIFIC CAPACITY TO BETTER EDUCATE STUDENTS AND ADVANCE SCIENCE THROUGH INSTRUMENT DEVELOPMENT PROJECTS. THE GENERAL PUBLIC BY GAINING ACCESS TO STATE-OF-THE-ART MEASUREMENT TECHNIQUES THROUGH THE NCNR GENERAL USER PROGRAM AND NEW THERAPEUTICS THAT ARE ANTICIPATED TO RESULT FROM THESE CAPABILITIES.SUBRECIPIENT ACTIVITIES: THE RECIPIENT DOES NOT INTEND TO SUBAWARD FUNDS.
OpenAlex ID: W4407989140