Anti-HIV cyclotides from the Chinese medicinal herb Viola yedoensis.
Cyclotides are macrocyclic plant peptides characterized by a knotted arrangement of three disulfide bonds. They display a range of interesting bioactivities, including anti-HIV and insecticidal activities. More than 100 different cyclotides have been isolated from two phylogenetically distant plant families, the Rubiaceae and Violaceae. In this study we have characterized the cyclotides from Viola yedoensis, an important Chinese herb from the Violaceae family that has been reported to contain potential anti-HIV agents. From V. yedoensis five new and three known cyclotides were identified and shown to have anti-HIV activity. The most active of these is cycloviolacin Y5, which is one of the most potent of all cyclotides tested so far using in vitro XTT-based anti-HIV assays. Cycloviolacin Y5 is the most hydrophobic of the cyclotides from V. yedoensis. We show that there is a positive correlation between the hydrophobicity and the anti-HIV activity of the new cyclotides and that this trend tracks with their ability to disrupt membranes, as judged from hemolytic assays on human erythrocytes.
Wang
Conan K L
CK
Institute for Molecular Bioscience, Australian Research Council Special Research Centre for Functional and Applied Genomics, University of Queensland, Brisbane, Australia.
Colgrave
Michelle L
ML
Gustafson
Kirk R
KR
Ireland
David C
DC
Goransson
Ulf
U
Craik
David J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001315:Australia; D047169:Cyclotides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D047168:Cystine Knot Motifs; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry*; D011487:Protein Conformation; D011817:Rabbits; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein; D032413:Viola / Q000737:chemistry*
D019380:Anti-HIV Agents; D047169:Cyclotides; D004365:Drugs, Chinese Herbal; C527610:cycloviolacin Y4; C527609:cycloviolacin Y5; C091930:kalata B1