Peptide Transport through the Blood-Brain Barrier
Midterm rept. 1 Jul 1987-31 Dec 1988
CALIFORNIA UNIV LOS ANGELES DEPT OF MEDICINE
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Most neuropeptides are incapable of entering brain from blood owing to the presence of unique anatomical structures in the brain capillary wall, which makes up the blood-brain barrier BBB. Such neuropeptides could be introduced into the bloodstream by intranasal insufflation and , thus, could have powerful medicinal properties e.g., beta B-endorphin for the treatment of pain, vasopressin analogues for treatment of memory, ACTH analogues for treatment of post-traumatic epilepsy, should these peptides be capable of traversing the BBB. One such strategy for peptide delivery through the BBB is the development of chimeric peptides, which is the basis of the present contract. The production of chimeric peptides involves the covalent coupling of an nontransportable peptide e.g., B-endorphin, vasopressin to a transportable vector peptide e.g., insulin, transferrin, cationized albumin, histone. The transportable peptide is capable of penetrating the BBB via receptor-mediated or absorptive-mediated transcytosis. Therefore, the introduction of chimeric peptides allows the nontransportable peptide to traverse the BBB via physiologic mechanisms by piggy back on the transportable Vector. Keywords Peptide transport, Chimeric peptides, Hybrid peptides.
- Anatomy and Physiology