The effect of beta-turn structure on the permeation of peptides across monolayers of bovine brain microvessel endothelial cells.
The effect of beta-turn structure on the permeation of peptides across monolayers of bovine brain microvessel endothelial cells.
复制标题
β-转角结构对肽跨牛脑微血管内皮细胞单层渗透的影响。
DOI：
10.1023/a:1012104301773
复制
发表时间：
1997
影响因子：
3.7
通讯作者：
Borchardt,RT
中科院分区：
文献类型：
--
作者：
Sorensen,M;Steenberg,B;Knipp,GT;Wang,W;Steffansen,B;Frokjaer,S;Borchardt,RT
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, anin vitromodel 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 Peffvalues was made for a series of model peptides. For the most hydrophobic peptides (Ac-PheProXaaIle-NH2and 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 Peffvalues 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/wvalues 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.
