Amphipathic Helical Glycopeptide Address Sequences for Enhanced Blood-Brain Barrier Transport of Neuroactive Peptides

University of Arizona researchers have successfully created a series of amphipathic helical glycopeptides with the ability to retain a membrane bound conformation promoting endocytosis as well as a water-soluble conformation facilitating exit from the membrane. This "biousian" property is intrinsic in allowing the molecule to traverse the blood brain barrier, and to "hop" from membrane to membrane. As a result, the researchers were able to generate a glycopeptide that can serve as a carrier molecule for use in a variety of pharmaceuticals based on endogenous neuropeptide transmitters.

Background:
A common difficulty in targeting drug delivery to the brain is the inability of large chemical compounds to cross the blood brain barrier. Inventors have devised a helical glycopeptide carrier molecule with the ability to traverse the blood brain barrier enabling its use in a variety of pharmaceuticals. While 50% of alpha helices are known to be amphipathic and therefore potential transporters, the molecule must also retain a membrane bound conformation to promote endocytosis as well as a water-soluble conformation to facilitate exit from the membrane.

Applications:

• Targeted drug delivery across the blood brain barrier
• Carrier molecule for a range of pharmaceuticals to treat anxiety, depression or neurodegenerative diseases

Advantages:

• Amphipathic helical glycopeptide carrier molecule with ability to penetrate the blood brain barrier, providing greater efficacy at lower drug dosage
• Dynamic "biousian" structure is intrinsic in allowing molecule to traverse the blood brain barrier and to "hop" from membrane to membrane
• Ability to deliver greater drug efficacy with fewer adverse side effects, such as addiction liability, or compromise of cardio-vascular, respiratory, immune and gastrointestinal systems

Status: issued U.S. patent #7,803,764