Isolation, characterization, and bioactivity of cyclotides from the Micronesian plant Psychotria leptothyrsa.
Cyclotides, the largest known family of head-to-tail cyclic peptides, have approximately 30 amino acid residues with a complex structure containing a circular peptide backbone and a cystine knot. They are found in plants from the Violaceae and Rubiaceae families and are speculated to function in plant protection. In addition to their insecticidal properties, cyclotides display cytotoxic, anti-HIV, antimicrobial, and inhibition of neurotensin binding activities. Although cyclotides are present in all violaceous species hitherto screened, their distribution and expression in Rubiaceae are not fully understood. In this study, we show that Psychotria leptothyrsa var. longicarpa (Rubiaceae) contains a suite of different cyclotides. The cyclotide fractions were isolated by RP-HPLC, and sequences of six new peptides, named psyles A-F, were determined by MS/MS sequencing. One of these, psyle C, is the first rubiaceous linear variant known. Psyles A, C, and E were analyzed in a fluorometric microculture assay to determine cytotoxicity toward the human lymphoma cell line U937-GTB. The IC(50) values of psyles A, C, and E were 26, 3.50, and 0.76 muM, respectively. This study expands the number of known rubiaceous cyclotides and shows that the linear cyclotide maintains cytotoxicity.
Gerlach
Samantha L
SL
Department of Ecology and Evolutionary Biology, Tulane University, 6823 St. Charles Avenue, New Orleans, LA 70118, USA. sgerlach@tulane.edu
Burman
Robert
R
Bohlin
Lars
L
Mondal
Debasis
D
Göransson
Ulf
U
D000595:Amino Acid Sequence; D047169:Cyclotides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D047168:Cystine Knot Motifs; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008849:Micronesia; D008969:Molecular Sequence Data; D010946:Plants, Medicinal / Q000737:chemistry*; D019666:Rubiaceae / Q000737:chemistry*
D047169:Cyclotides; C551603:psyle A; C551602:psyle C; C551604:psyle E