Constrained tryptophan-based oligomers for intracellular and CNS drug delivery. (FWOTM897)

The design of drug-conjugates able to enter cells represents a frontier challenge in the development of bioactive compounds targeting intracellular processes. The lipophilic nature of cellular membranes constitutes an impermeable barrier for hydrophilic therapeutic agents and prevents polar bioactive molecules such as peptides, proteins, and oligonucleotides from efficient cell entry. In order to address this major limitation, the current project aims to develop constrained tryptophan(Trp)-based oligomers (‘transport vectors’) for improved cell uptake and blood-brain barrier (BBB) permeation. Preliminary results showed that a family of dipeptidomimetic repeats, encompassing Trp analogues, were able to internalize cells with much higher efficiency than positive controls such as penetratin and octa-arginine. Moreover, promising data were obtained in
a BBB permeation assay. These results form a basis for the development of improved peptidomimetic vectors, capable to translocate various hydrophilic cargoes across biological membranes. The application potential of the vectors will be scoped through use of nucleoside-, peptide- and protein-based bioactive compounds, to be linked to the developed transport vectors.

Keywords:Chemistry, TRYPTOPHAN ANALOGUES

Disciplines:Physical chemistry not elsewhere classified