Síntese, caracterização e estudos estruturais de análogos do peptídeo antimicrobiano Cn-AMP1 em meios biomiméticos
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2015-07-31
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Universidade Federal de Goiás
Resumo
Antimicrobial peptides are part of the innate defense of several
organisms, and represent candidate drugs in their natural form, allowing for the
development of modified peptides with improved pharmacological profiles. In
this context, this study aimed of the synthesis of Cn-AMP1, an antimicrobial
peptide naturally isolated from green coconut water, which has activity against
fungi, gram-positive and gram-negative bacterias well as effects on the
proliferation of cancer cells and low toxicity to mammalian cells, the analogs
[Trp9] Cn-AMP1 and [Gly9] Cn-AMP1 were also obtained by solid phase peptide
synthesis using the Fmoc strategy. The characterization and purification of the
peptides were performed by mass spectrometry and high-performance liquid
chromatography. Structural studies of the peptides were performed by circular
dichroism (CD) and nuclear magnetic resonance (NMR) in the presence of
biomimetic enviroments. CD and NMR results indicated that the peptides do not
present preferential conformations in aqueous solutions, however adopt helical
conformations in membrane mimetic environments. CD studies have shown that
Cn-AMP1 and [Gly9] Cn-AMP1 do not adopt show defined conformation in the
presence of DPC micelles at different pH values, however the peptide [Trp9] Cn-
AMP1 showed a small a-helical content in the presence of 100mM DPC. In the
presence of SDS the spectra of all peptides showed helical profiles at both pH
4, pH 7 as well as in the absence of buffer. NMR experiments indicated the
interaction of the peptides [Trp9] Cn-AMP1 and [Gly9] Cn-AMP1 with SDS
micelles at pH 4 (25 °C), and structural calculations indicated that [Trp9]Cn-
AMP1 adopts an α-helical conformation between Val2-Gly8, and that [Gly9] Cn-
AMP1 adopts an α -helical conformation between Val2-Arg5. Dynamic light
scattering and zeta potential experiments were performed to investigate the
effect of addition of peptides into phospholipid vesicles. All of the peptides
caused variations on the POPC:POPG (3:1) and POPC, LUVs hydrodynamic
radios, however major changes were observed for the anionic vesicles due to
the strong interaction between the arginine residue of the peptides and the
negativelly charge of membrane.
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MATOS, C. O. Síntese, caracterização e estudos estruturais de análogos do peptídeo antimicrobiano Cn-AMP1 em meios biomiméticos. 2015. 108 f. Dissertação (Mestrado em Química) - Universidade Federal de Goiás, Goiânia, 2015.