The cyclotide fingerprint in oldenlandia affinis: elucidation of chemically modified, linear and novel macrocyclic peptides

Chembiochem. 2007 Jun 18;8(9):1001-11. doi: 10.1002/cbic.200700097.

Abstract

The complete suite of cyclotides present in Oldenlandia affinis (Rubiaceae), the plant that was originally found to contain this unique family of circular proteins, has been characterised. This study expands the number of known cyclotides in this plant to 17, of which nine new sequences (kalata B9-B17) were characterised in this work. In addition, five derivatives that contain oxidation products of the conserved tryptophan were identified, and it was shown that the formation of these derivatives is catalysed by exposure to sunlight. Furthermore, we describe two "linear" cyclotide analogues. These acyclic peptides have three intact disulfide bonds, and their N and C termini coincide with the hypothesised cleavage sites from the precursor protein. This work increases our knowledge about the sequence variation that is accommodated by the cyclic cystine knot scaffold, confirms its applicability as a template for drug design, and also shows the first natural degradation pathways for cyclotides. These pathways have important implications for the persistence and environmental fate of the cyclotides if used as crop-protection agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Alkylation
  • Amino Acid Sequence
  • Amino Acids / analysis
  • Chromatography, High Pressure Liquid
  • Cyclotides / biosynthesis
  • Cyclotides / chemistry*
  • Disulfides / chemistry
  • Hemolysis / drug effects
  • Lysine / chemistry
  • Macrocyclic Compounds / chemistry*
  • Mass Spectrometry
  • Molecular Sequence Data
  • Molecular Weight
  • Oldenlandia / chemistry*
  • Oxidation-Reduction
  • Peptide Mapping
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrophotometry, Ultraviolet
  • Tryptophan / chemistry

Substances

  • Amino Acids
  • Cyclotides
  • Disulfides
  • Macrocyclic Compounds
  • kalata B1
  • Tryptophan
  • Lysine