title: Identification and characterization of a bactericidal and proapoptotic peptide from Cycas revoluta seeds with DNA binding properties.
abstract: Nowadays, novel pharmacies have been screened from plants. Among them are the peptides, which show multiple biotechnological activities. In this report, a small peptide (Ala-Trp-Lys-Leu-Phe-Asp-Asp-Gly-Val) with a molecular mass of 1,050 Da was purified from Cycas revoluta seeds by using reversed-phase liquid chromatography. This peptide shows clear deleterious effects against human epidermoid cancer (Hep2) and colon carcinoma cells (HCT15). It caused inhibition of cancer cell proliferation and further disruption of nucleosome structures, inducing apoptosis by direct DNA binding. A remarkable antibacterial activity was also observed in this same peptide. Nevertheless, no significant lysis of normal RBC cells was observed in the presence of peptide. Additionally, an acetylation at the N-termini portion is able to reduce both activities. Bioinformatics tools were also utilized for construction of a three-dimensional model showing a single amphipathic helix. Since in vitro binding studies show that the target of this peptide seems to be DNA, theoretical docking studies were also performed to better understand the interaction between peptide and nucleic acids and also to shed some light on the acetyl group role. Firstly, binding studies showed that affinity contacts basically occur due to electrostatic attraction. The complex peptide-ssDNA was clearly oriented by residues Ala(1), Lys(3), and Asp(6), which form several hydrogen bonds that are able to stabilize the complex. When acetyl was added, hydrogen bonds are broken, reducing the peptide affinity. In summary, it seems that information here provided could be used to design a novel derivative of this peptide which a clear therapeutic potential.
authors: Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555, USA.
authors: Santi M
authors: SM
authors: Mandal
authors: Ludovico
authors: L
authors: Migliolo
authors: Subhasis
authors: S
authors: Das
authors: Mahitosh
authors: M
authors: Mandal
authors: Octavio L
authors: OL
authors: Franco
authors: Tapas K
authors: TK
authors: Hazra
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000302:isolation & purification*; D000970:Antineoplastic Agents / Q000302:isolation & purification*; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell; D002453:Cell Cycle; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms; D029784:Cycas; D004268:DNA-Binding Proteins / Q000302:isolation & purification*; D006801:Humans; D008958:Models, Molecular; D009707:Nucleosomes / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D010936:Plant Extracts / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D012639:Seeds; D020539:Sequence Analysis, Protein
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D009707:Nucleosomes; D010455:Peptides; D010936:Plant Extracts