Limits...
New linear antiplasmodial peptides related to angiotensin II.

Silva AF, Torres MD, Silva Lde S, Alves FL, Pinheiro AA, Miranda A, Capurro ML, Oliveira VX - Malar. J. (2015)

Bottom Line: The 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.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.The hydrophobic portion and the arginine, tyrosine, proline, and phenylalanine, when present on peptide primary sequence, tend to increase the antiplasmodial activity.

View Article: PubMed Central - PubMed

Affiliation: Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Rua Santa Adélia, 166, Santo André, SP, 09210-170, Brazil. adrianafarias.silva@gmail.com.

ABSTRACT

Background: 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 angiotensin II cannot be used as an anti-malarial drug.

Methods: This 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.

Results: The 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.

Conclusions: The 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 invasion.

No MeSH data available.


Related in: MedlinePlus

Effects of Ang II, peptides 5 and 6 in contractile responses by muscle tissue incubation compared to carbachol (CCh) activity. Triple asterisk statistically significant compared with control value p < 0.05 (mean ± standard deviation, n = 2)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4634797&req=5

Fig6: Effects of Ang II, peptides 5 and 6 in contractile responses by muscle tissue incubation compared to carbachol (CCh) activity. Triple asterisk statistically significant compared with control value p < 0.05 (mean ± standard deviation, n = 2)

Mentions: Results obtained in the contractile response assays showed that out of the two peptides tested, none presented contractile activity compared to Ang II and carbachol (Fig. 6).Fig. 6


New linear antiplasmodial peptides related to angiotensin II.

Silva AF, Torres MD, Silva Lde S, Alves FL, Pinheiro AA, Miranda A, Capurro ML, Oliveira VX - Malar. J. (2015)

Effects of Ang II, peptides 5 and 6 in contractile responses by muscle tissue incubation compared to carbachol (CCh) activity. Triple asterisk statistically significant compared with control value p < 0.05 (mean ± standard deviation, n = 2)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4634797&req=5

Fig6: Effects of Ang II, peptides 5 and 6 in contractile responses by muscle tissue incubation compared to carbachol (CCh) activity. Triple asterisk statistically significant compared with control value p < 0.05 (mean ± standard deviation, n = 2)
Mentions: Results obtained in the contractile response assays showed that out of the two peptides tested, none presented contractile activity compared to Ang II and carbachol (Fig. 6).Fig. 6

Bottom Line: The 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.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.The hydrophobic portion and the arginine, tyrosine, proline, and phenylalanine, when present on peptide primary sequence, tend to increase the antiplasmodial activity.

View Article: PubMed Central - PubMed

Affiliation: Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Rua Santa Adélia, 166, Santo André, SP, 09210-170, Brazil. adrianafarias.silva@gmail.com.

ABSTRACT

Background: 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 angiotensin II cannot be used as an anti-malarial drug.

Methods: This 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.

Results: The 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.

Conclusions: The 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 invasion.

No MeSH data available.


Related in: MedlinePlus