NDLI: The Effect of β-Turn Structure on the Permeation of Peptides Across Monolayers of Bovine Brain Microvessel Endothelial Cells

Content Provider	Springer Nature Link
Author	Sorensen, Mette Steenberg, Betina Knipp, Gregory T. Wang, Wen Steffansen, Bente Frokjaer, Sven Borchardt, Ronald T.
Copyright Year	1997
Abstract	Purpose. To investigate the effects of the β-turn structure of a peptide on its permeation via the paracellular and transcellular routes across cultured bovine brain microvessel endothelial cell (BBMEC) monolayers, an in vitro model of the blood-brain barrier (BBB). Methods. The effective permeability coefficients (P$_{eff}$) of the model peptides were determined across BBMEC monolayers. The dimensions of the aqueous pores in the tight junctions (TJs) of the BBMEC monolayers were determined using a series of hydrophilic permeants. This value and the molecular radius of each peptide were used to calculate the theoretical paracellular (P$_{P}$ $^{}$) and transcellular (P$_{T}$ $^{}$) permeability coefficients for each peptide. Results. A comparison of the theoretical P$_{P}$ $^{*}$ values with the observed P$_{eff}$ values was made for a series of model peptides. For the most hydrophobic peptides (Ac-PheProXaaIle-NH$_{2}$ and Ac-PheProXaaIleVal-NH$_{2}$; Xaa = Gly, Ile), it was concluded that the Gly-containing peptide of each pair more readily permeates BBMEC monolayers via the transcellular pathway than the Ile-containing analog. In addition, the Gly-containing peptides, which exhibit more β-turn structure, were shown to be more lipophilic than the Ile-containing peptides as estimated by the log of their l-octanol:HBSS partition coefficients (log P$_{o/w}$). However, the three hydrophilic peptide pairs (Ac-TyrProXaaAspVal-NH$_{2}$, Ac-TyrProXaaAsnVal-NH$_{2}$, and Ac-TyrProXaaIleVal-NH$_{2}$; Xaa = Gly, Ile) were found to permeate BBMEC monolayers predominantly via the paracellular pathway. No differences were observed in the P$_{eff}$ values of the hydrophilic peptides having higher β-turn structures as compared to the peptides lacking these structural features. In addition, the Ile-containing peptides exhibited significantly higher log P$_{o/w}$ values than the Gly-containing hydrophilic peptides. Conclusions. Hydrophobic peptides that exhibit significant β-turn structure in solution are more lipophilic as measured by log P$_{o/w}$, and more readily permeate BBMEC monolayers via the transcellular route than hydrophobic peptides that lack this type of solution structure. Similar secondary structural features in hydrophilic peptides do not appear to sufficiently alter the physicochemical properties of the peptides so as to alter their paracellular flux through BBMEC monolayers.
Starting Page	1341
Ending Page	1348
Page Count	8
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	14
Issue Number	10
e-ISSN	1573904X
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	1997-01-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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