caa a22 4500 477127274 CHVBK 20180405111653.0 cr unu---uuuuu 170330e19971001xx s 000 0 eng 10.1023/A:1012104301773 doi (NATIONALLICENCE)springer-10.1023/A:1012104301773 The Effect of β-Turn Structure on the Permeation of Peptides Across Monolayers of Bovine Brain Microvessel Endothelial Cells [Elektronische Daten] [Mette Sorensen, Betina Steenberg, Gregory Knipp, Wen Wang, Bente Steffansen, Sven Frokjaer, Ronald Borchardt] 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 (Peff) 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 (PP *) and transcellular (PT *) permeability coefficients for each peptide. Results. A comparison of the theoretical PP * values with the observed Peff values was made for a series of model peptides. For the most hydrophobic peptides (Ac-PheProXaaIle-NH2 and Ac-PheProXaaIleVal-NH2; 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 Po/w). However, the three hydrophilic peptide pairs (Ac-TyrProXaaAspVal-NH2, Ac-TyrProXaaAsnVal-NH2, and Ac-TyrProXaaIleVal-NH2; Xaa = Gly, Ile) were found to permeate BBMEC monolayers predominantly via the paracellular pathway. No differences were observed in the Peff 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 Po/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 Po/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. Plenum Publishing Corporation, 1997 peptide delivery nationallicence transcellular diffusion nationallicence solution conformation nationallicence BBMEC monolayers nationallicence bovine brain microvessel endothelial cells, passive diffusion nationallicence Sorensen Mette Department of Pharmaceutics, The Royal Danish School of Pharmacy, Copenhagen, Denmark aut Steenberg Betina Department of Pharmaceutics, The Royal Danish School of Pharmacy, Copenhagen, Denmark aut Knipp Gregory Department of Pharmaceutical Chemistry, The University of Kansas, 2095 Constant Ave., 66047, Lawrence, Kansas aut Wang Wen Department of Pharmaceutical Chemistry, The University of Kansas, 2095 Constant Ave., 66047, Lawrence, Kansas aut Steffansen Bente Department of Pharmaceutics, The Royal Danish School of Pharmacy, Copenhagen, Denmark aut Frokjaer Sven Department of Pharmaceutics, The Royal Danish School of Pharmacy, Copenhagen, Denmark aut Borchardt Ronald Department of Pharmaceutical Chemistry, The University of Kansas, 2095 Constant Ave., 66047, Lawrence, Kansas aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/10(1997-10-01), 1341-1348 0724-8741 14:10<1341 1997 14 11095 https://doi.org/10.1023/A:1012104301773 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012104301773 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sorensen Mette Department of Pharmaceutics, The Royal Danish School of Pharmacy, Copenhagen, Denmark aut NATIONALLICENCE 700 1- Steenberg Betina Department of Pharmaceutics, The Royal Danish School of Pharmacy, Copenhagen, Denmark aut NATIONALLICENCE 700 1- Knipp Gregory Department of Pharmaceutical Chemistry, The University of Kansas, 2095 Constant Ave., 66047, Lawrence, Kansas aut NATIONALLICENCE 700 1- Wang Wen Department of Pharmaceutical Chemistry, The University of Kansas, 2095 Constant Ave., 66047, Lawrence, Kansas aut NATIONALLICENCE 700 1- Steffansen Bente Department of Pharmaceutics, The Royal Danish School of Pharmacy, Copenhagen, Denmark aut NATIONALLICENCE 700 1- Frokjaer Sven Department of Pharmaceutics, The Royal Danish School of Pharmacy, Copenhagen, Denmark aut NATIONALLICENCE 700 1- Borchardt Ronald Department of Pharmaceutical Chemistry, The University of Kansas, 2095 Constant Ave., 66047, Lawrence, Kansas aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/10(1997-10-01), 1341-1348 0724-8741 14:10<1341 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer