title: N-methyl phenylalanine-rich peptides as highly versatile blood-brain barrier shuttles.
abstract: Here we studied the capacity of N-MePhe-(N-MePhe)(3)-CONH(2), Cha-(N-MePhe)(3)-CONH(2), and 2Nal-(N-MePhe)(3)-CONH(2) to carry various drugs (cargos) in in vitro blood-brain barrier (BBB) models in order to determine the versatility of these peptides as BBB-shuttles for drug delivery to the brain. Using SPPS, the peptides were coupled to GABA, Nip, and ALA to examine their passive BBB permeation by means of PAMPA and their lipophilicity by IAMC. Unaided, these nonpermeating drugs alone did not cross the PAMPA barrier and the BBB passively; however, the peptides tested as potential BBB shuttles transferred them by passive transfer through the PAMPA phospholipid. The permeability of peptides that showed the highest permeability in PAMPA, and Ac-N-MePhe-(N-MePhe)(3)-CONH(2) as the parent peptide was also examined in bovine brain microvessel endothelial cells (BBMECs). These peptide-based BBB shuttles open up the possibility to overcome the formidable obstacle of the BBB, thereby achieving drug delivery to the brain.
authors.affiliation: Institute for Research in Biomedicine Barcelona, Barcelona Science Park, Baldiri Reixac 10, E-08028 Barcelona, Spain.
authors.forename: Morteza
authors.initials: M
authors.lastname: Malakoutikhah
authors.forename: Roger
authors.initials: R
authors.lastname: Prades
authors.forename: Meritxell
authors.initials: M
authors.lastname: Teixidó
authors.forename: Ernest
authors.initials: E
authors.lastname: Giralt
mesh_terms: D000622:Aminolevulinic Acid / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001692:Biological Transport; D001808:Blood Vessels / Q000166:cytology; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000098:blood supply; D002417:Cattle; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D018920:Coculture Techniques; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D013058:Mass Spectrometry; D015394:Molecular Structure; D009557:Nipecotic Acids / Q000737:chemistry / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000737:chemistry / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D009557:Nipecotic Acids; D009842:Oligopeptides; C030278:nipecotic acid; C034515:phenylalanine methyl ester; D010649:Phenylalanine; D005680:gamma-Aminobutyric Acid; D000622:Aminolevulinic Acid