Highly potential antiplasmodial restricted peptides.

Autor: Marcelo Der Torossian T; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, Brazil., Silva AF, Alves FL, Capurro ML, Miranda A, Vani Xavier O Jr
Jazyk: angličtina
Zdroj: Chemical biology & drug design [Chem Biol Drug Des] 2015 Feb; Vol. 85 (2), pp. 163-71. Date of Electronic Publication: 2014 Jul 11.
DOI: 10.1111/cbdd.12354
Abstrakt: Malaria is an infectious disease responsible for approximately one million deaths annually. The antimalarial effects of angiotensin II and its analogs against Plasmodium gallinaceum and P. falciparum have recently been reported. To evaluate antiplasmodial activity, we synthesized five angiotensin II-restricted analogs containing disulfide bridges. To accomplish this, peptides containing two inserted amino acid residues (cysteine) were synthesized by the Fmoc solid-phase method, purified by liquid chromatography, and characterized by mass spectrometry. Conformational studies were performed by circular dichroism. The results indicated that two of the analogs had higher antiplasmodium activity (92% and 98% activity) than angiotensin II (88% activity), measured by fluorescence microscopy. Results showed that the insertion position must be selected, to preserve the hydrophobic interactions between the non-polar residues, as this affects antiplasmodial activity. The circular dichroism studies suggested that the active analogs as well as the native angiotensin II adopt a β-turn conformation in different solutions. This approach provided 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.
(© 2014 John Wiley & Sons A/S.)
Databáze: MEDLINE
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