Invited Speaker 7th Modern Solid Phase Peptide Synthesis & Its Applications Symposium 2019

MiniChlorotoxins and MiniApamins, Blood-Brain Barrier Peptide Shuttles Derived From Venoms. (#8)

Meritxell Teixido 1
  1. IRB Barcelona, Barcelona, Spain

Brain delivery is one of the major challenges in drug development because of the high number of patients suffering from central nervous diseases (CNS) and the low efficiency of treatments available. Although the blood–brain barrier (BBB) prevents most drugs from reaching their targets, BBB-shuttle peptides offer great promise to safely overcome this formidable obstacle. Peptides which are experiencing a golden era are receiving growing attention because of their lower cost, reduced immunogenicity, and higher chemical versatility than traditional Trojan horse antibodies to be used as BBB-shuttles, as we have recently reviewed.[1-3]

Over the last years, we have reported the use of BBB-shuttles inspired in peptides found in venoms. We have minimized apamin, a neurotoxin from bee venom, by reducing its complexity, toxicity and immunogenicity, while preserving brain targeting, active transport, and protease-resistance leading to MiniAp-4. [4,5]

More recently we discovered new family of peptides able to cross the BBB, MiniChlorotoxins (MiniCTXs) derived from Chlorotoxin (CTX), a disulphide-rich stable peptide found in the venom of the Israeli scorpion Leirus quinquestriatus, which is able to enter the brain and bind specifically to tumour tissue. MiniCTXs are the result of the research performed to decipher the minimal part of CTX that maintains transport capacity and but abolishing its toxicity.[6]

  1. B. Oller-Salvia, M. Sánchez-Navarro, E. Giralt, M. Teixidó Chem. Soc. Rev. (2016), 45, 4690-4707.
  2. M. Sánchez-Navarro, E. Giralt, M. Teixidó Curr. Opin. Chem. Biol. (2017), 38, 134-140.
  3. M. Sánchez-Navarro, M. Teixidó, E. Giralt Acc. Chem. Res. (2017), 50, 1847-1854.
  4. B. Oller-Salvia, M. Sánchez-Navarro, S. Ciudad, M. Guiu, P. Arranz-Gibert, C. Garcia, R.R. Gomis, R. Cecchelli, J. García, E. Giralt, M. Teixidó Angew. Chem. Int. Ed. (2016), 55, 572-575.
  5. C. Fuster, M. Varese, J. García, E. Giralt, M. Sánchez‐Navarro, M. Teixidó J. Pept. Sci. (2019) e3172.
  6. C. Dıaz-Perlas, M. Varese, S. Guardiola, J. García, M. Sánchez-Navarro, E. Giralt, M. Teixidó Chem. Commun. (2018) 54, 12738-1274.