title: Isolation and characterization of cytotoxic cyclotides from Viola philippica.
abstract: Cyclotides are a large family of plant peptides characterized by a macrocyclic backbone and knotted arrangement of three disulfide bonds. This unique structure renders cyclotides exceptionally stable to thermal, chemical and enzymatic treatments. They exhibit a variety of bioactivities, including uterotonic, anti-HIV, cytotoxic and hemolytic activity and it is these properties that make cyclotides an interesting peptide scaffold for drug design. In this study, eight new cyclotides (Viphi A-H), along with eight known cyclotides, were isolated from Viola philippica, a plant from the Violaceae family. In addition, Viba 17 and Mram 8 were isolated for the first time as peptides. The sequences of these cyclotides were elucidated primarily by using a strategy involving reduction, enzymatic digestion and tandem mass spectroscopy sequencing. Several of the cyclotides showed cytotoxic activities against the cancer cell lines MM96L, HeLa and BGC-823. The novel cyclotides reported here: (1) enhance the known sequence variation observed for cyclotides; (2) extend the number of species known to contain cyclotides; (3) provide interesting structure-activity relationships that delineate residues important for cytotoxic activity. In addition, this study provides insights into the potential active ingredients of traditional Chinese medicines.
authors: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, 132# Lanhei Road, Heilongtan, Kunming 650204, Yunnan, PR China.
authors: Wenjun
authors: W
authors: He
authors: Lai Yue
authors: LY
authors: Chan
authors: Guangzhi
authors: G
authors: Zeng
authors: Norelle L
authors: NL
authors: Daly
authors: David J
authors: DJ
authors: Craik
authors: Ninghua
authors: N
authors: Tan
mesh_terms: D000595:Amino Acid Sequence; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D047169:Cyclotides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship; D032413:Viola / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D047169:Cyclotides