Applying the Retro‐Enantio Approach To Obtain a Peptide Capable of Overcoming the Blood–Brain Barrier

Abstract

The blood-brain barrier (BBB) is af ormidable physical and enzymatic barrier that tightly controls the passage of molecules from the blood to the brain. In fact, less than 2% of all potential neurotherapeutics are able to cross it. Here,by applying the retro-enantio approach to ap eptide that targets the transferrin receptor,afull protease-resistant peptide with the capacity to act as aB BB shuttle was obtained and thus enabled the transport of av ariety of cargos into the central nervous system.

Lipid Bilayer Crossing—The Gate of Symmetry. Water-Soluble Phenylproline-Based Blood-Brain Barrier Shuttles

“…Then, a modified version of our conjugates, containing a small linker selectively cleaved in the brain and located in between the BBB shuttle and the cargo, could selectively release the drug in the CNS. Finally, the use of non-natural amino acids (and in some cases also the use of the d -amino acid version) has been shown in the literature to increase the resistance to proteolytic cleavage. − Thus, although not reported in this paper, one could speculate about the possibility of oral administration of these new PhPro-based conjugates.…”

“…Finally, the use of non-natural amino acids (and in some cases also the use of the D-amino acid version) has been shown in the literature to increase the resistance to proteolytic cleavage. [73][74][75] Thus, although not reported in this paper, one could speculate about the possibility of oral administration of these new PhPro-based conjugates.…”

Bike peptides: a ride through the membrane

“…One of the most important challenges in medicinal chemistry is identifying molecules with the ability to permeate across biological barriers or to increase the transport of cargoes through them. Various examples of molecules with this capacity have been reported, including cyclic and N ‐methylated polypeptides, among others . The use of a staple motif is focused mostly on fixing a particular conformation of a peptide, for instance, the α ‐helix, thereby improving the pharmacologic parameters that also trigger biological activities .…”

Toxins and derivatives in molecular pharmaceutics: Drug delivery and targeted therapy

“…The engineered analogs not only effec-1220 tively inhibited the human Cav2.2 channels, but also demonstrated im-1221 proved serum stability. It is envisioned that our knowledge on toxins will expand more rap- with all-D amino acids [213][214][215]. 1307 The process of drug development is becoming more and more chal- [110] A.G. de Boer, P.J.…”