{"doi":"10.3390/life15101568","title":"Design, Structural Stability, Membrane Binding, and Antibacterial Activity of Novel Antimicrobial Peptides Derived from Wuchuanin-A1","abstract":"Antibiotic resistance is a major health problem globally, highlighting the need for alternative antimicrobials that may potentially reduce the emergence of resistance compared to conventional antibiotics. Antimicrobial peptides (AMPs) are promising candidates because of their broad-spectrum activity. In this study, we designed three derivatives (i.e., Analog-1, -2, and -3) of the native peptide, Wuchuanin-A1, for improving their antibacterial activity against Staphylococcus aureus and Escherichia coli. The hypothesis is that the antibacterial activity of these peptides can be improved by increasing their amphipathicity (evaluated using hydrophobic moment analysis), α-helical stability, and membrane binding properties. In this case, the residues of native peptide were mutated to form an amphipathic peptide, referred to here as Analog-1. Then, the N- and C-termini of Analog-1 were capped with acetyl and amide groups, respectively, to produce Analog-2. Finally, the Asp and Arg residues in Analog-2 were mutated to Glu and Lys residues, respectively, in Analog-3. Circular dichroism (CD) spectra in trifluoroethanol (TFE) or methanol (MeOH) showed that Analog-3 has the highest α-helical stability, followed by Analog-2 and Analog-1. Two-dimensional nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics (MD) simulations studies indicated that Analog-2 and -3 have a stable continuous α-helical structure. Both Analog-2 and -3 can form dimer or oligomer at higher concentrations. All three analogs can bind to model membranes of Gram-positive and Gram-negative bacteria, with Analog-3 as the best membrane binding affinity through Langmuir monolayer analysis. Both Analog-2 and -3 have better antibacterial activities against S. aureus and E. coli compared to Analog-1 and the native peptide, with minimum inhibitory concentration (MIC) values 3.91 µg/mL against S. aureus and 62.5 µg/mL against E. coli, which are 2–32-fold lower than those of Analog-1. In addition, Analog-2 and -3 have better activity against S. aureus than E. coli bacteria. We proposed that the increase in antibacterial activity of Analog-2 and -3 was due to the α-helical stability, amphipathic structure, and membrane binding properties.","journal":"Life","year":2025,"id":522191,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9462,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1394172,"name":"Ahmad Habibie","orcid":null,"position":1,"is_corresponding":false},{"id":528484,"name":"Prajnaparamita Dhar","orcid":"0000-0002-5821-5253","position":2,"is_corresponding":false},{"id":56687,"name":"Krzysztof Kuczera","orcid":"0000-0003-2358-1349","position":3,"is_corresponding":false},{"id":1393593,"name":"Respati Tri Swasono","orcid":"0000-0003-0762-6930","position":4,"is_corresponding":false},{"id":1393594,"name":"Muhammad Saifur Rohman","orcid":"0000-0002-7764-9778","position":5,"is_corresponding":false},{"id":1393595,"name":"Tri Joko Raharjo","orcid":"0000-0003-0615-5241","position":6,"is_corresponding":false},{"id":236270,"name":"Teruna J. Siahaan","orcid":"0000-0001-7250-0627","position":7,"is_corresponding":false},{"id":1394171,"name":"Rizki A. Putri","orcid":null,"position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:49:54.058858Z","pmid":"41157240","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}