DO CELL-PENETRATING PEPTIDES CROSS THE BLOOD-BRAIN BARRIER?
| Autor: | Stalmans, S., Wynendaele, E., Bracke, N., Bart De Spiegeleer |
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| Zdroj: | ResearcherID JOURNAL OF PEPTIDE SCIENCE |
| ISSN: | 1075-2617 |
| Popis: | Cell-penetrating peptides (CPPs) are a chemically diverse group of peptides, able to cross cell membranes. In literature, several studies are available describing a successful coupling of a brain-impermeable compound to a CPP to transport the molecule across the blood-brain barrier (BBB). Quantitative kinetic BBB transport studies of cell-penetrating peptides are however not yet available. To characterize quantitatively the BBB behavior of CPPs, the in vivo BBB transport and the in vitro metabolic stability of a diverse set of CPPs was determined. The chemical-functional space of the CPPs was first explored using chemo-molecular descriptors and a newly defined cell-penetrating response [1]. Then, five chemically and functionally diverse CPPs were selected representing the CPP space. Their BBB influx and efflux was quantified, as well as their distribution to the brain capillaries and parenchyma. Furthermore, the in vitro metabolic stability of these CPPs in mouse serum and brain was determined to ensure the reliability of our BBB transport conclusions. Finally, preliminary results of the in-brain region distribution will be presented. Our results indicate that the investigated CPPs show divergent BBB transport kinetics, which may be explained by their structural difference and their mechanism of cellular influx. |
| Databáze: | OpenAIRE |
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