Potential therapeutic applications of the cyclotides and related cystine knot mini-proteins.
Cyclotides are naturally occurring mini-proteins that have a cyclic peptide backbone and a knotted arrangement of three disulfide bonds. They are remarkably stable and have a diverse range of therapeutically useful biological activities, including antimicrobial and anti-HIV activity, although their natural function appears to be as plant defence agents. Cyclotides are amenable to chemical synthesis and the potential exists to graft new bioactivities onto their cyclic cystine knot framework as a way of stabilising peptide drugs. Over the last few years, proof-of-concept that bioactive peptide epitopes can be grafted onto cyclotides and related cystine knot mini-proteins has been obtained. The cystine knot framework is tolerant to a wide range of residue substitutions and is showing great promise as a scaffold in drug design and protein engineering.
Craik
David J
DJ
University of Queensland, Institute for Molecular Bioscience, Australian Research Council Special Research Centre for Functional and Applied Genomics, Brisbane QLD 4072, Australia. d.craik@imb.uq.edu.au
Clark
Richard J
RJ
Daly
Norelle L
NL
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D047169:Cyclotides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D003545:Cysteine / Q000737:chemistry*; D047168:Cystine Knot Motifs; D004337:Drug Carriers; D015195:Drug Design; D006801:Humans; D007306:Insecticides / Q000494:pharmacology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D015202:Protein Engineering
D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D047169:Cyclotides; D004337:Drug Carriers; D007306:Insecticides; D003545:Cysteine