Cyclotides, a versatile ultrastable micro-protein scaffold for biotechnological applications

Bioorg Med Chem Lett. 2017 Dec 1;27(23):5089-5099. doi: 10.1016/j.bmcl.2017.10.051. Epub 2017 Oct 21.

Abstract

Cyclotides are fascinating microproteins (≈30-40 residues long) with a unique head-to-tail cyclized backbone, stabilized by three disulfide bonds forming a cystine knot. This unique topology makes them exceptionally stable to chemical, thermal and biological degradation compared to other peptides of similar size. Cyclotides have been also found to be highly tolerant to sequence variability, aside from the conserved residues forming the cystine knot, able to cross cellular membranes and modulate intracellular protein-protein interactions both in vitro and in vivo. These properties make them ideal scaffolds for many biotechnological applications. This article provides and overview of the properties of cyclotides and their applications as molecular imaging agents and peptide-based therapeutics.

Keywords: Bioimaging agents; Circular protein; Cyclotide; Cystine knot; Drug design; Kalata B1; MCoTI-I.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Contrast Media / chemistry
  • Cyclotides / chemistry*
  • Cyclotides / genetics
  • Cyclotides / metabolism
  • Drug Design
  • Plant Proteins / chemistry
  • Plant Proteins / genetics
  • Plant Proteins / metabolism
  • Positron Emission Tomography Computed Tomography
  • Protein Structure, Tertiary
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry

Substances

  • Contrast Media
  • Cyclotides
  • Plant Proteins
  • Recombinant Proteins
  • kalata B1
  • trypsin inhibitor MCoTI-II