PeptAIDes

Under the contribution of the ZK-81B project PeptAIDes, a study was recently published by the ACS Chemical Biology Journal (Impact Factor 5, Q1 in Biochemistry & Mol. Medicine). The structure-function-relationship of the unique cyclic cystine-rich knot (CCK) motif in cyclotides was evaluated . The anti-proliferative bioactivity on activated immune cells of T20K is strongly dependent on the native CCK motif and cystine-knot or acyclic variants lost antiproliferative activity. The structural motif was identified as detrimental for cell penetration into mammalian cells, since only the native peptide but no truncated variants showed transport across biological membranes. Structural studies have further underlined the importance of the CCK for structure and function of anti-proliferative T20K – a drug candidate in clinical phase studies for the therapy of Multiple Sclerosis.

The study was carried out at the Institute of Pharmacology (Medical University of Vienna) and by the contribution of collaboration partner from the University of Basel, the University of Freiburg and the University of Queensland.

Hellinger, R., Muratspahić, E., Devi, S., Koehbach, J., Vasileva, M., Harvey, PJ., Craik, DJ., Gründemann, C., and Gruber, CW. Importance of the cyclic cystine knot structural motif for immunosuppressive effects of cyclotides, 2021, ACS Chem Bio, in press, doi: 10.1021/acschembio.1c00524.