Abstract
BackgroundAntiplasmodial activities of angiotensin II and its analogues have been extensively investigated in Plasmodium gallinaceum and Plasmodium falciparum parasite species. Due to its vasoconstrictor property angiotensin II cannot be used as an anti-malarial drug.MethodsThis work presents the solid-phase syntheses and liquid chromatography and mass spectrometry characterization of ten linear peptides related to angiotensin II against mature P. gallinaceum sporozoites and erythrocyte invasion by P. falciparum. Conformational analyses were performed by circular dichroism. IC50 assays were performed to identify the ideal concentration used on the biological tests and haemolytical erythrocytic assays were made to verify the viability of the biological experiments. The contractile responses of the analogues were made to evaluate if they are promising candidates to be applied as antiplasmodial drugs.ResultsThe results indicate two short-peptides constituted by hydrophobic residues (5 and 6) with antiplasmodial activity in these models, 89 and 94 % of biological activity against P. gallinaceum sporozoite, respectively, and around 50 % of activity against P. falciparum. Circular dichroism spectra suggested that all the peptides adopted β-turn conformation in different solutions, except peptide 3. Besides the biological assays IC50, the haemolysis assays and contractile response activities were applied for peptides 5 and 6, which did not present expressive results.ConclusionsThe hydrophobic portion and the arginine, tyrosine, proline, and phenylalanine, when present on peptide primary sequence, tend to increase the antiplasmodial activity. This class of peptides can be explored, as anti-malarial drugs, after in vivo model tests.Graphical abstract:The most active peptide presented 94 % activity on P. gallinaceum sporozoites and 53 % inhibited P. falciparum ring forms invasionElectronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0974-y) contains supplementary material, which is available to authorized users.
Highlights
Antiplasmodial activities of angiotensin II and its analogues have been extensively investigated in Plasmodium gallinaceum and Plasmodium falciparum parasite species
These analogues were purified and characterized as described in Methods, Effect of te peptides on salivary gland‐derived Plasmodium gallinaceum sporozoites The effect of the peptides on sporozoites was determined in vitro by fluorescence microscopy after one hour of incubation of the parasites with each peptide in the presence of propidium iodide
New peptides related to angiotensin II (Ang II) were designed, including the most hydrophobic amino acid residues (Val, Ile, Pro, and Phe), aromatic residues (Tyr, His, Pro, and Phe) and residues from the Ang II hydrophobic cluster (Tyr, Ile and His) in an attempt to verify the peptide-parasite interactions
Summary
Antiplasmodial activities of angiotensin II and its analogues have been extensively investigated in Plasmodium gallinaceum and Plasmodium falciparum parasite species. Due to its vasoconstrictor property, Ang II cannot be used as an anti-malarial drug regardless of its antiplasmodial activity (in vitro assays) in Plasmodium gallinaceum sporozoites [1] and Plasmodium falciparum [6]. Chamlian et al [2] studied some lactam bridged Ang II analogues, which presented Asp and Lys insertion in order to restrict the peptide They observed that VC-12 (Asp-Arg-Val-Tyr-Ile-Asp-His-Lys-Pro-Phe) and VC-26 (Asp-Arg-Val-Tyr-Asp-Ile-His-Lys-Pro-Phe) analogues showed relevant antiplasmodial activity against P. gallinaceum sporozoite, 87 and 73 %, respectively. In order to understand the role of each amino acid and its side chain, Silva et al [3] and Ferreira et al [4] proposed different modifications in the Ang II molecule. They replaced each amino acid by Ala [4] or deleted the
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
