Abstract
Cyclotides are plant-derived peptides found within five families of flowering plants (Violaceae, Rubiaceae, Fabaceae, Solanaceae, and Poaceae) that have a cyclic backbone and six conserved cysteine residues linked by disulfide bonds. Their presence within the Violaceae species seems ubiquitous, yet not all members of other families produce these macrocyclic peptides. The genus Palicourea Aubl. (Rubiaceae) contains hundreds of neotropical species of shrubs and small trees; however, only a few cyclotides have been discovered hitherto. Herein, five previously uncharacterized Möbius cyclotides within Palicourea sessilis and their pharmacological activities are described. Cyclotides were isolated from leaves and stems of this plant and identified as pase A–E, as well as the known peptide kalata S. Cyclotides were de novo sequenced by MALDI-TOF/TOF mass spectrometry, and their structures were solved by NMR spectroscopy. Because some cyclotides have been reported to modulate immune cells, pase A–D were assayed for cell proliferation of human primary activated T lymphocytes, and the results showed a dose-dependent antiproliferative function. The toxicity on other nonimmune cells was also assessed. This study reveals that pase cyclotides have potential for applications as immunosuppressants and in immune-related disorders.
Highlights
The genus Palicourea Aubl. (Rubiaceae) contains hundreds of neotropical species of shrubs and small trees; only a few cyclotides have been discovered hitherto
Brazil has the largest biodiversity in the world and is an ideal “playground” for phytochemists to discover peptides from plants, there are still few studies describing the isolation of cyclotides from Brazilian plants.[16,46−51] The relative lack of study of cyclotides in Brazilian plants probably reflects an earlier focus among Brazilian researchers on nonpeptidic natural products based on available training and equipment, but with opportunities for international internships in cyclotide-specialist laboratories, as occurred in this project, cyclotide research is expanding in Brazil
Dried leaves and stems of P. sessilis were extracted as described in the Experimental Section
Summary
The genus Palicourea Aubl. (Rubiaceae) contains hundreds of neotropical species of shrubs and small trees; only a few cyclotides have been discovered hitherto. The leaves and stems of P. sessilis (Rubiaceae) were investigated allowing the identification and the characterization of five new Möbius cyclotides (pase A−E). The similarities of pase peptides with T20K prompted us to investigate their immunosuppressant activity on human peripheral blood mononuclear cells (PBMCs).
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