Part:BBa_K3096015

pVEC - a cell penetrating peptide

pVEC (peptide vascular endothelial-cadherin) is a cell-penetrating peptide, which transports proteins through coadministration.

Biology & Usage

Through their penetrating activity, Cell penetrating peptides can be utilised as carriers of small therapeutic macromolecules across membranes, eg. Insulin across rat intestinal cells (Kamei et al.). Since cytotoxic effects, induced by the disintegration of the plasma membrane, have occured, improvement and development of cell penetrating peptides is necessary.

pVEC is derived from a segment of the transmembrane domain part of a murine vascular endothelial-cadherin protein, which is involved in cell-cell adhesion (Elmquist et al.). Its ability to enter the cell can mostly be explained by the N-terminal stretch of hydrophobic amino acids, which interact with the plasma membrane (Elmquist et al.). It was shown by Kamei et al., that the coadministration of pVEC with Insulin increases its intestinal uptake in rat cells, suggesting it a suitable tool for the oral delivery route of drugs.

Sequence and Features

pVEC consists of a stretch of 18 amino acids, with the N-terminal hydrophobic amino acids being crucial determinants of the uptake. We propose future iGEM Teams to improve this part by exchanging Arg6, Arg8 or Ser17 by alanine. According to Elmquist et al., this is supposed to increase the penetrating activity.

Assembly Compatibility:

• 10
  COMPATIBLE WITH RFC[10]
• 12
  COMPATIBLE WITH RFC[12]
• 21
  COMPATIBLE WITH RFC[21]
• 23
  COMPATIBLE WITH RFC[23]
• 25
  COMPATIBLE WITH RFC[25]
• 1000
  COMPATIBLE WITH RFC[1000]

Characterisation by iGEM Tuebingen 2019

Team iGEM Tuebingen 2019 has added and characterised pVEC by building a software tool which evaluates the penetrability of CPPs, comparing their activity. The results of the characterisation are shown in Fig. 1, where common or new CPPs are shown with their respective penetrability.

References

1. Kamei, Noriyasu, et al. "Usefulness of cell-penetrating peptides to improve intestinal insulin absorption." Journal of Controlled Release 132.1 (2008): 21-25.
2. Elmquist, Anna, Mats Hansen, and Ülo Langel. "Structure–activity relationship study of the cell-penetrating peptide pVEC." Biochimica et Biophysica Acta (BBA)-Biomembranes 1758.6 (2006): 721-729.