Membrane-active peptides (MAPs) possess unique properties that make them valuable tools for studying membrane structure and function and promising candidates for therapeutic applications. This review paper provides an overview of the fundamental aspects of MAPs, focusing on their membrane interaction mechanisms and potential applications. MAPs exhibit various structural features, including amphipathic structures and specific amino acid residues, enabling selective interaction with multiple membranes. Their mechanisms of action involve disrupting lipid bilayers through different pathways, depending on peptide properties and membrane composition. The therapeutic potential of MAPs is significant. They have demonstrated antimicrobial activity against bacteria and fungi, making them promising alternatives to conventional antibiotics. MAPs can selectively target cancer cells and induce apoptosis, opening new avenues in cancer therapeutics. Additionally, MAPs serve as drug delivery vectors, facilitating the transport of therapeutic cargoes across cell membranes. They represent a fascinating class of biomolecules with significant potential in basic research and clinical applications. Understanding their mechanisms of action and designing peptides with enhanced selectivity and efficacy will further expand their utility in diverse fields. Exploring MAPs holds promise for developing novel therapeutic strategies against infections, cancer, and drug delivery challenges.
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http://dx.doi.org/10.3390/pharmaceutics15082091 | DOI Listing |
ACS Infect Dis
January 2025
Department of Chemistry, University of Waterloo, 200 University Ave. West, Waterloo, Ontario N2L3G1, Canada.
The calcium-dependent antibiotics (CDAs) are a group of seven closely related membrane-active cyclic lipopeptide antibiotics (cLPAs) first isolated in the early 1980s from the fermentation broth of . Their target was unknown, and the mechanism of action is uncertain. Herein, we report new routes for the synthesis of CDA4b and its analogues, explore the structure-activity relationships at its lipid tail and at positions 3, 9, and 11, and determine the CDAs' lipid target.
View Article and Find Full Text PDFJ Phys Chem B
January 2025
Department of Applied Science, William & Mary, Williamsburg, Virginia 23185, United States.
Lysophospholipids (LPLs) and host defense peptides (HDPs) are naturally occurring membrane-active agents that disrupt key membrane properties, including the hydrocarbon thickness, intrinsic curvature, and molecular packing. Although the membrane activity of these agents has been widely examined separately, their combined effects are largely unexplored. Here, we use experimental and computational tools to investigate how lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE), an LPL of lower positive spontaneous curvature, influence the membrane activity of piscidin 1 (P1), an α-helical HDP from fish.
View Article and Find Full Text PDFToxins (Basel)
October 2024
Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Key Laboratory of Genetic Evolution & Animal Models, Sino-African Joint Research Center, and New Cornerstone Science Laboratory, Kunming Institute of Zoology, The Chinese Academy of Sciences, No.17 Longxin Road, Kunming 650201, China.
Spider venoms are emerging as a rich source of bioactive peptide toxins with therapeutic potential. Lynx spiders of the genus are small, cursorial hunters that employ complex venom to subdue arthropod prey. However, extracting crude venom from these diminutive arachnids poses significant challenges.
View Article and Find Full Text PDFBiophys Chem
February 2025
Departamento de Química, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 39100-000 Diamantina, MG, Brazil. Electronic address:
Here we present studies of the structure and membrane interactions of ecPis-4 s, a new antimicrobial peptide from the piscidin family, which shows a wide-range of potential biotechnological applications. In order to understand the mode of action ecPis-4 s, the peptide was chemically synthesized and structural investigations in the presence of anionic POPC:POPG (3:1, mol:mol) membrane and SDS micelles were performed. CD spectroscopy demonstrated that ecPis-4 s has a high content of helical structure in both membrane mimetic media, which is in line with solution NMR spectroscopy that revealed an amphipathic helical conformation throughout the entire peptide chain.
View Article and Find Full Text PDFSci Rep
November 2024
Department of Chemistry, King's College London, London, UK.
Optical monitoring of peptide binding to live cells is hampered by the abundance of naturally occurring fluorophores such as tryptophan. Unnatural amino acids incorporating synthetic fluorophores such as BODIPY overcome these optical limitations. A drawback to using fluorophores in lipid binding peptide design is their propensity to override other interactions, potentially causing the peptides to lose their binding selectivity.
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