Oral Presentation 10th Australian Peptide Conference 2013

Future of Peptides as Blood-Brain Barrier Shuttles (#28)

Meritxell Teixido 1 , Ernest Giralt 1 2
  1. IRB Barcelona, Barcelona, Spain
  2. Organic Chemistry, University of Barcelona, Barcelona, Spain

Over recent years we have worked extensively on the use of peptides as BBB-shuttles to carry drugs that cannot cross the blood-brain barrier (BBB) and therefore cannot reach the brain unaided. The capacity of a drug to cross the BBB is crucial, as several major diseases require brain treatment. These include neurodegenerative disorders such as Parkinson’s and Alzheimer’s, but also central nervous system (CNS) diseases, such as schizophrenia, epilepsy and bipolar disorder. Cerebral cancer, HIV, and some aspects of obesity can also be included as pharmaceutical targets inside the brain.1

Initially, we focused our efforts on passive diffusion as a transport mechanism.2,3,4 In these studies, we achieved molecules with 2-4 amino acids that act as passive BBB-shuttles and are efficient at carrying drugs such as L-Dopa, Baicalin, GABA, Nipecotic and Aminolevulinic acids. In some cases, the shuttle plays a dual role and once inside the brain acts as an enzyme inhibitor.5 In spite of their potential use for small molecules, passive diffusion shuttles have limitations for transporting macromolecules (proteins, mAbs, nanoparticles). This prompted us more recently to focus on the use of peptides recognized by receptors as actively transported BBB-shuttles6,7 and study their ability to carry antibodies through this barrier.

In our quest for novel BBB shuttle candidates, we have been interested in studying animal venoms that have been reported to affect the CNS without disrupting the BBB. Designing non toxic analogs of these peptides that have the BBB transport capacity but are non toxic is one of our recent sources of BBB-shuttles that we are developing.

In this communication, we will review our latest results of peptides as passive BBB-shuttles and present our unpublished results on peptide-shuttles that use active transport to cross the blood-brain barrier.

  1. - Malakoutikhah M.; Teixidó, M. ; Giralt, E. Angew. Chem. Int. Ed. 2011, 50, 7998-8014.
  2. - Teixidó M. Zurita, E.; Malakoutikhah, M.; Tarrago, T.; Giralt, E. JACS 2007, 129, 11802-11813.
  3. - Malakoutikhah M.; Teixidó, M.; Giralt, E. J.Med.Chem. 2008, 51, 4884-4889.
  4. - Malakoutikhah M.; Prades, R.; Teixidó, M.; Giralt, E. J.Med.Chem. 2010, 53, 2354-2363.
  5. - Teixidó M.; Zurita, E.; Mendieta, L.; Tarrago, T.; Giralt, E. Biopolymers Pept.Sci. 2013, in press.
  6. - Prades R.; Guerrero, S.; Araya, E.; Teixidó, M.; Kogan, M.J.; Giralt, E. Biomaterials 2012, 33, 7194-7205.
  7. - Oller-Salvia, B.; Teixidó, M.; Giralt, E.; Biopolymers Pept. Sci., 2013, in press.