Effects of Amino Acid Deletion on the Antiplasmodial Activity of Angiotensin II

Autor(es)

Rodrigues Ferreira, Luiz Henrique ^[1] ; Silva, Adriana Farias ^[1] ; Torossian Torres, Marcelo Der ^[1] ; Pedron, Cibele Nicolaski ^[1] ; Capurro, Margareth Lara ^[2] ; Alves, Flavio Lopes ^[3] ; Miranda, Antonio ^[3] ; Oliveira, Jr., Vani Xavier ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210170 Santo Andre, SP - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Biomed, BR-05508 Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Biofis, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS; v. 20, n. 4, p. 553-564, DEC 2014.
• Citações Web of Science: 2

Resumo

Malaria is an infectious disease for which effective treatment and prevention strategies remain limited. Our group recently reported that angiotensin II (AII) presents antiplasmodial activity and inhibits the development of Plasmodium gallinaceum in Aedes aegypti. However, details concerning role of each amino acid residue in the antiplasmodial activity of the peptide and information about the minimal structure responsible for this activity remain unknown. In this work, we investigated the effects of specific deletions (i.e., mono-, di-, tri- and tetra-deletions) of AII amino acids on the antiplasmodial activity of this molecule. The peptides were synthesized on solid phase method using the t-Boc strategy, purified using high performance liquid chromatography and characterized using mass spectrometry. The lytic activity of the peptides was assessed in vitro using mature sporozoites extracted from the salivary glands of infected Aedes aegypti mosquitoes. The results demonstrate that all of the deletions reduced antiplasmodial activity compared to native AII and that active analogs tend to adopt beta-turn conformations; however, the deletion of bulky hydrophobic residues causes greater reductions of bioactivity than the deletion of hydrophilic residues. Corroborating previous studies, we observed that analog extremities are susceptible to changes and can be carefully modified without compromising the activity of this compound. This research contributes to our understanding of the role of each AII amino acid residue in activity against Plasmodium gallinaceum and identifies two short analogs with similar antiplasmodial activity to AII. These analogs may be candidates for additional antimalarial assays because they are inexpensive and easy to synthesize. (AU)

• Processo FAPESP: 11/15083-3 - Antimaláricos Cíclicos Derivados da Angiotensina II
• Beneficiário: Marcelo Der Torossian Torres
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 11/10823-9 - Compostos antimaláricos derivados da angiotensina II
• Beneficiário: Vani Xavier de Oliveira Junior
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 08/51869-9 - Uma nova perspectiva na prevencao e no tratamento quimioterapico da malaria.
• Beneficiário: Vani Xavier de Oliveira Junior
• Modalidade de apoio: Auxílio à Pesquisa - Regular