Cyclotides as templates in drug design.
Cyclotides are remarkably stable proteins from plants that have a range of pharmaceutical and agricultural applications based on both their various bioactivities and their potential for use as stable protein-engineering templates. This article discusses literature on pharmaceutically relevant activities of cyclotides, including anti-HIV, antimicrobial and cytotoxic activities, and evaluates their potential therapeutic applications. Their applications as templates for the design of antiangiogenic agents for the treatment of cancer and as anti-infective agents are also described. Toxic effects of cyclotides, whose native function is as insecticidal agents, can be removed by simple mutagenesis, thus rationalizing the apparent conundrum of proposing insecticidal agents as leads for human therapeutics.
Henriques
Sónia Troeira
ST
The University of Queensland, Institute for Molecular Bioscience, Brisbane, QLD 4072, Australia.
Craik
David J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D057005:Bioengineering / Q000379:methods; D047169:Cyclotides / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009496:Neurotensin / Q000037:antagonists & inhibitors
D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D000972:Antineoplastic Agents, Phytogenic; D047169:Cyclotides; D009496:Neurotensin