| Full text | |
| Author(s): |
Torres, Marcelo Der Torossian
[1]
;
Silva, Adriana Farias
[1]
;
Alves, Flavio Lopes
[2]
;
Capurro, Margareth Lara
[3]
;
Miranda, Antonio
[2]
;
Oliveira Junior, Vani Xavier
[1]
Total Authors: 6
|
| Affiliation: | [1] Univ Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210170 Santo Andre, SP - Brazil
[2] Univ Fed Sao Paulo, Dept Biofis, Sao Paulo - Brazil
[3] Univ Fed Sao Paulo, Inst Ciencias Biomed 2, Sao Paulo - Brazil
Total Affiliations: 3
|
| Document type: | Journal article |
| Source: | INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS; v. 20, n. 3, p. 277-287, SEP 2014. |
| Web of Science Citations: | 8 |
| Abstract | |
Malaria is caused by the protozoa Plasmodium and is responsible for approximately one million deaths annually. The antimalarial effects of angiotensin II and its analogs against Plasmodium gallinaceum and falciparum have recently been reported. Here, 12 angiotensin II restricted analogs that contain i - (i + 2), i - (i + 3) and i - (i + 4) lactam bridges were synthesized to analyze their effect on antiplasmodial activity. To accomplish this, peptides containing two amino acid residues (aspartic or glutamic acids and lysine or ornithine), were synthesized by the t-Boc solid phase method, purified by liquid chromatography, and characterized by mass spectrometry, and conformational studies were performed by circular dichroism. The results indicate that some of the analogs had anti-plasmodium activity similar to angiotensin II (88 % activity). Among those, eight compounds exhibited high activity (> 70 %), measured by fluorescence microscopy. The analogs with smaller lactam rings and an aspartic acid residue as the bridgehead element had lower levels of lytic activity. The results obtained with the new restricted analogs showed that the insertion position (near the N-terminus), the ring size, and the number of residues between the rings are as important as the components of lactam bridge, regardless of their chirality. The circular dichroism studies suggest that the active analogs, and native angiotensin II, adopt a beta-fold conformation in different solutions. In conclusion, this approach provides insight for understanding the effects of restricting the ring size and position on the bioactivity of angiotensin II and provides a new direction for the design of potential chemotherapeutic agents. (AU) | |
| FAPESP's process: | 11/15083-3 - Cyclic Antimalariais Derivates of Angiotensin II |
| Grantee: | Marcelo Der Torossian Torres |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 11/10823-9 - Antimalarial compounds derivative from angiotensin II |
| Grantee: | Vani Xavier de Oliveira Junior |
| Support Opportunities: | Regular Research Grants |