Planta Med 2008; 74 - SL65
DOI: 10.1055/s-0028-1083945

NMR studies, solid phase synthesis and MD/SA simulation as a tool for structural elucidation of new bioactive peptides from the latex of Jatropha curcas l

WF Altei 1, DG Picchi 1, SC Barbosa 2, EM Cilli 2, MJ Giannini 3, EM Cardoso-Lopes 4, MCM Young 4, LB Torres 4, GM Giesel 5, H Verli 5, VS Bolzani 1
  • 1Núcleo de Bioensaio, Biossíntese e Ecofisiologia de Produtos Naturais (NuBBE)
  • 2Departamento de Bioquímica e Biotecnologia, IQ-UNESP, Araraquara, SP
  • 3Faculdade de Ciências Farmacêuticas, Araraquara, SP
  • 4Instituto de Botânica, secretaria do meio Ambiente, São Paulo, SP
  • 5Faculdade de Farmácia – UFRGS, Porto Alegre, RS, Brazil

In a previous investigation on Euphorbiaceous plant species we have isolated cyclic peptides from the latex of Jatropha multifida. In continuing this investigation aiming new bioactive peptides from plants, we have studied the latex of Jatropha curcas L. The dried latex of this species was partitioned with ethyl acetate, fractioned on Sephadex G15, eluted in solid phase extraction (SEPACK-C18), and purified by HPLC to yield the novel jatrophidin I (1) and the known pohlianin A (2). The characterization of the new compound was performed by amino acid analysis, mass spectroscopy, and 1D and 2D NMR studies. The peptide 1 exists as a cyclic structure GWLNLLGP, which was confirmed by synthesis using the Fmoc strategy. Considering the conformational equilibrium of proline residues between cis and trans forms, this peptide would have more than one conformational states in solution. The work accomplished to provide additional information to conformational equilibrium through Molecular Dynamics/Simulated Annealing (MD/SA) simulations considered this peptide with proline in both cis and trans orientations. In fact, this experiment showed more signals than the expected at the region N-H, which may be due to the presence of two conformers, cis-Pro and trans-Pro. Thus, based on the employed protocol it was possible to describe the occurrence of two main conformers for jatrophidin I, corroborating previous structure elucidated by NMR studies. The new cyclic peptide showed week antifungal effect against Candida albicans, C. krusei, C. parapsilosis and Cryptococcus neoformans, as well as a moderate activity as an acetylcholinesterase inhibitor, when compared with the standard galanthamine.

Acknowledgements: BIOTA-FAPESP, CAPES and CNPq for financial support.