{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T13:25:58Z","timestamp":1773581158254,"version":"3.50.1"},"reference-count":61,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>The membrane-active nature of phospholipase A2-derived peptides makes them potential candidates for antineoplastic and antibacterial therapies. Two short 13-mer C-terminal fragments taken from snake venom Lys49-PLA2 toxins (p-AppK and p-Acl), differing by a leucine\/phenylalanine substitution, were synthesized and their bioactivity was evaluated. Their capacity to interfere with the survival of Gram-positive and Gram-negative bacteria as well as with solid and liquid tumors was assessed in vitro. Toxicity to red blood cells was investigated via in silico and in vitro techniques. The mode of action was mainly studied by molecular dynamics simulations and membrane permeabilization assays. Briefly, both peptides have dual activity, i.e., they act against both bacteria, including multidrug-resistant strains and tumor cells. All tested bacteria were susceptible to both peptides, Pseudomonas aeruginosa being the most affected. RAMOS, K562, NB4, and CEM cells were the main leukemic targets of the peptides. In general, p-Acl showed more significant activity, suggesting that phenylalanine confers advantages to the antibacterial and antitumor mechanism, particularly for osteosarcoma lines (HOS and MG63). Peptide-based treatment increased the uptake of a DNA-intercalating dye by bacteria, suggesting membrane damage. Indeed, p-AppK and p-Acl did not disrupt erythrocyte membranes, in agreement with in silico predictions. The latter revealed that the peptides deform the membrane and increase its permeability by facilitating solvent penetration. This phenomenon is expected to catalyze the permeation of solutes that otherwise could not cross the hydrophobic membrane core. In conclusion, the present study highlights the role of a single amino acid substitution present in natural sequences towards the development of dual-action agents. In other words, dissecting and fine-tuning biomembrane remodeling proteins, such as snake venom phospholipase A2 isoforms, is again demonstrated as a valuable source of therapeutic peptides.<\/jats:p>","DOI":"10.3390\/cimb44010004","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T10:24:52Z","timestamp":1640168692000},"page":"46-62","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Lessons from a Single Amino Acid Substitution: Anticancer and Antibacterial Properties of Two Phospholipase A2-Derived Peptides"],"prefix":"10.3390","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4637-4468","authenticated-orcid":false,"given":"Jos\u00e9 R.","family":"Almeida","sequence":"first","affiliation":[{"name":"Universidad Regional Amaz\u00f3nica Ikiam, Km 7 Via Muyuna, Tena 150150, Ecuador"}]},{"given":"Bruno","family":"Mendes","sequence":"additional","affiliation":[{"name":"Universidad Regional Amaz\u00f3nica Ikiam, Km 7 Via Muyuna, Tena 150150, Ecuador"},{"name":"Departmento de Bioqu\u00edmica e Biologia Tecidual, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas 13083-862, SP, Brazil"}]},{"given":"Marcelo","family":"Lancellotti","sequence":"additional","affiliation":[{"name":"Departmento de Bioqu\u00edmica e Biologia Tecidual, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas 13083-862, SP, Brazil"},{"name":"Faculdade de Ci\u00eancias Farmac\u00eauticas, Universidade Estadual de Campinas (UNICAMP), Campinas 13083-871, SP, Brazil"}]},{"suffix":"Jr.","given":"Gilberto C.","family":"Franchi","sequence":"additional","affiliation":[{"name":"Centro Integrado de Pesquisas Oncohematologicas da Infancia, Universidade Estadual de Campinas (UNICAMP), Campinas 13083-881, SP, Brazil"}]},{"given":"\u00d3scar","family":"Passos","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, Rua Campo Alegre s\/n, 4169-007 Porto, Portugal"}]},{"given":"Maria J.","family":"Ramos","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, Rua Campo Alegre s\/n, 4169-007 Porto, Portugal"}]},{"given":"Pedro A.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, Rua Campo Alegre s\/n, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5996-2621","authenticated-orcid":false,"given":"Cl\u00e1udia","family":"Alves","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, Rua Campo Alegre s\/n, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1283-1042","authenticated-orcid":false,"given":"Nuno","family":"Vale","sequence":"additional","affiliation":[{"name":"OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"Department of Community Medicine, Information and Health Decision Sciences (MEDCIDS), Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6018-4724","authenticated-orcid":false,"given":"Paula","family":"Gomes","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, Rua Campo Alegre s\/n, 4169-007 Porto, Portugal"}]},{"given":"Saulo L.","family":"da Silva","sequence":"additional","affiliation":[{"name":"Universidad Regional Amaz\u00f3nica Ikiam, Km 7 Via Muyuna, Tena 150150, Ecuador"},{"name":"LAQV\/REQUIMTE, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, Rua Campo Alegre s\/n, 4169-007 Porto, Portugal"},{"name":"Faculty of Chemical Sciences, University of Cuenca, Cuenca 010107, Ecuador"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tornesello, A.L., Borrelli, A., Buonaguro, L., Buonaguro, F.M., and Tornesello, M.L. 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