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Here, we performed in vitro assays of Pa-MAP, Pa-MAP1.9, and Pa-MAP2 synthetic polyalanine peptides derived from the polar fish Pleuronectes americanus toward Trypanosoma cruzi, T. brucei gambiense and Plasmodium falciparum activities. We demonstrated that the peptides Pa-MAP1.9 and Pa-MAP2 were effective to inhibit T. brucei growth. In addition, structural analyses using molecular dynamics (MD) studies showed that Pa-MAP2 penetrates deeper into the membrane and interacts more with phospholipids than Pa-MAP1.9, corroborating the previous in vitro results showing that Pa-MAP1.9 acts within the cell, while Pa-MAP2 acts via membrane lysis. In conclusion, polyalanine Pa-MAP1.9 and Pa-MAP2 presented activity against bloodstream forms of T. b. gambiense, thus encouraging further studies on the application of these peptides as a treatment for sleeping sickness.<\/jats:p>","DOI":"10.3390\/md21080434","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T10:00:15Z","timestamp":1690797615000},"page":"434","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Anti-Protozoan Activities of Polar Fish-Derived Polyalanine Synthetic Peptides"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6027-9109","authenticated-orcid":false,"given":"Ellynes Amancio Correia","family":"Nunes","sequence":"first","affiliation":[{"name":"Postgraduate Program in Biochemistry, Federal University of Rio Grande do Norte, Natal 59078-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Cl\u00e1udia","family":"da Silva","sequence":"additional","affiliation":[{"name":"S-Inova Biotech, Graduate Program in Biotechnology, Dom Bosco Catholic University, Campo Grande 79117-900, Brazil"},{"name":"Department of Biochemistry and Immunology, Faculty of Medicine of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Sao Paulo 14040-900, Brazil"},{"name":"Laboratory of Research in Virology and Immunology, Institute of Biological and Health Sciences, Federal University of Alagoas, Maceio 57020-600, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6676-5362","authenticated-orcid":false,"given":"Marlon Henrique","family":"Cardoso","sequence":"additional","affiliation":[{"name":"S-Inova Biotech, Graduate Program in Biotechnology, Dom Bosco Catholic University, Campo Grande 79117-900, Brazil"},{"name":"Center for Proteomics and Biochemical Analysis, Catholic University of Bras\u00edlia, Brasilia 71966-700, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3289-7513","authenticated-orcid":false,"given":"Sergio Leandro Esp\u00edndola","family":"Preza","sequence":"additional","affiliation":[{"name":"S-Inova Biotech, Graduate Program in Biotechnology, Dom Bosco Catholic University, Campo Grande 79117-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucas Silva","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Protein Chemistry, Department of Cell Biology, Institute of Biological Sciences, University of Bras\u00edlia, Brasilia 73345-010, Brazil"},{"name":"UMR 7245 Mol\u00e9cules de Communication et Adaptation des Micro-Organismes, Mus\u00e9um National d\u2019Histoire Naturelle, CNRS, 75005 Paris, France"},{"name":"Graduate Program in Molecular Pathology, University of Brasilia, Brasilia 73345-010, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Breno Emanuel Farias","family":"Frihling","sequence":"additional","affiliation":[{"name":"S-Inova Biotech, Graduate Program in Biotechnology, Dom Bosco Catholic University, Campo Grande 79117-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9364-7289","authenticated-orcid":false,"given":"S\u00e9bastien Olivier","family":"Charneau","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Protein Chemistry, Department of Cell Biology, Institute of Biological Sciences, University of Bras\u00edlia, Brasilia 73345-010, Brazil"},{"name":"Graduate Program in Molecular Pathology, University of Brasilia, Brasilia 73345-010, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Grellier","sequence":"additional","affiliation":[{"name":"UMR 7245 Mol\u00e9cules de Communication et Adaptation des Micro-Organismes, Mus\u00e9um National d\u2019Histoire Naturelle, CNRS, 75005 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9546-0525","authenticated-orcid":false,"given":"Oct\u00e1vio Luiz","family":"Franco","sequence":"additional","affiliation":[{"name":"S-Inova Biotech, Graduate Program in Biotechnology, Dom Bosco Catholic University, Campo Grande 79117-900, Brazil"},{"name":"Center for Proteomics and Biochemical Analysis, Catholic University of Bras\u00edlia, Brasilia 71966-700, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6606-2189","authenticated-orcid":false,"given":"Ludovico","family":"Migliolo","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Biochemistry, Federal University of Rio Grande do Norte, Natal 59078-900, Brazil"},{"name":"S-Inova Biotech, Graduate Program in Biotechnology, Dom Bosco Catholic University, Campo Grande 79117-900, Brazil"},{"name":"Postgraduate Program in Cellular and Molecular Biology, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1016\/S0140-6736(09)60233-6","article-title":"Rescuing the bottom billion through control of neglected tropical diseases","volume":"373","author":"Hotez","year":"2009","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.idc.2012.03.002","article-title":"Leishmaniasis worldwide and global estimates of its incidence","volume":"26","author":"Rassi","year":"2012","journal-title":"Infect. 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