The relationship between peptide structure and transport across epithelial cell monolayers

Burton, Philip S.; Conradi, Robert A.; Hilgers, Allen R.; Ho, Norman F.H.; Maggiora, Linda

doi:10.1016/0168-3659(92)90067-2

Cited by 106 publications

(67 citation statements)

References 21 publications

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“…Interacting with the lipid phase peptides may translocate through membrane by forming pores or inverted micelles or diffuse through the bilayer (11). Peptide diffusion has been considered as improbable because it requires high desolvation energy (53,54). Another model proposes that hydrophilic CPPs translocate across the membrane by forming pores through oligomerization of several peptide molecules.…”

Section: Discussionmentioning

confidence: 99%

Translocation of Dynorphin Neuropeptides across the Plasma Membrane

Marinova

Vukojević

Surcheva

et al. 2005

Journal of Biological Chemistry

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Several peptides, including penetratin and Tat, are known to translocate across the plasma membrane. Dynorphin opioid peptides are similar to cell-penetrating peptides in a high content of basic and hydrophobic amino acid residues. We demonstrate that dynorphin A and big dynorphin, consisting of dynorphins A and B, can penetrate into neurons and non-neuronal cells using confocal fluorescence microscopy/immunolabeling. The peptide distribution was characterized by cytoplasmic labeling with minimal signal in the cell nucleus and on the plasma membrane. Translocated peptides were associated with the endoplasmic reticulum but not with the Golgi apparatus or clathrin-coated endocytotic vesicles. Rapid entry of dynorphin A into the cytoplasm of live cells was revealed by fluorescence correlation spectroscopy. The translocation potential of dynorphin A was comparable with that of transportan-10, a prototypical cell-penetrating peptide. A central big dynorphin fragment, which retains all basic amino acids, and dynorphin B did not enter the cells. The latter two peptides interacted with negatively charged phospholipid vesicles similarly to big dynorphin and dynorphin A, suggesting that interactions of these peptides with phospholipids in the plasma membrane are not impaired. Translocation was not mediated via opioid receptors. The potential of dynorphins to penetrate into cells correlates with their ability to induce non-opioid effects in animals. Translocation across the plasma membrane may represent a previously unknown mechanism by which dynorphins can signal information to the cell interior.

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Section: Discussionmentioning

confidence: 99%

Translocation of Dynorphin Neuropeptides across the Plasma Membrane

Marinova

Vukojević

Surcheva

et al. 2005

Journal of Biological Chemistry

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“…The standard method for determination of hydrogen bonding (desolvation potential) involves measurement of the difference between the logarithms of the partition coefficients in a hydrogen bonding solvent (octanol) and a non-hydrogen bonding lipophilic organic solvent (isooctane) [14, 15, 16, 17, 18]. Implicit in this method is that the hydrophobic effects are similar in both organic solvent systems so that the difference in partitioning is explained by the ability of the organic solvent to accommodate the hydrogen bonding requirement of the solute, providing a direct measurement of the hydrogen bonding potential.…”

Section: Methodsmentioning

confidence: 99%

Differential Interactions of Urocortin/Corticotropin-Releasing Hormone Peptides with the Blood-Brain Barrier

Kastin

Akerstrom²

2002

Neuroendocrinology

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The two newest members of the urocortin (UCN)/corticotropin-releasing hormone (CRH) family of peptides – UCN II and UCN III – bind to the CRH-2 receptor, suppress feeding, and are expressed in the periphery as well as the brain. We used several sensitive techniques to examine their interactions with the blood-brain barrier (BBB). Of the four known peptides in this family, each interacts with the BBB differently. UCN I barely enters the brain from blood unless its latent saturable influx system is activated by leptin or pretreatment with glucose. However, neither leptin nor glucose affected the entry of intact UCN II. UCN II reached brain paranchyma at a moderate rate that was not self-inhibited or cross-inhibited by UCN/CRH peptides. The apparent, but misleading, rapid influx of UCN III (stresscopin) could be explained by degradation at the BBB itself. Influx of CRH into brain was slower than UCN II but faster than UCN I; it was inhibited by excess CRH but not by excess UCN I, II, III, or leptin. CRH is the only member of this family to have a saturable efflux system out of the brain. Determination of hydrogen bonding, newly applied here to ingestive peptides, was not helpful in explaining these differential interactions of the UCN peptides with the BBB.

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“…The difference logP C16/W − logP O/W (formally equal to logP C16/O ) is frequently considered an indicator of the hydrogen-bonding ability 65,[79][80][81] and, consequently, as a parameter characterizing the preferential location of the solutes in the bilayer. The fraction of compounds present in the core as a function of logP C16/O is plotted in Figure 4.…”

Section: Resultsmentioning

confidence: 99%

Partitioning of Organic Compounds in Phases Imitating the Headgroup and Core Regions of Phospholipid Bilayers

et al. 2006

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Solvation free energies of drugs, peptides, and other small molecules in the core and headgroup regions of phospholipid bilayers determine their conformations, accumulation, and transport properties. The transfer free energy includes the energy terms for the formation of a cavity for the solute, the interactions of the solute with phospholipids, electrostatic interactions of the solute with the membrane and dipole potentials, and entropy terms. The interaction energies with phospholipids can be estimated by correlating the partitioning in surrogate solvent systems and in the bilayer. As the headgroup surrogate, we use diacetylphosphatidylcholine (DAcPC), the acetylated headgroup of the most abundant mammalian phospholipid, phosphatidylcholine, which forms a homogeneous solution with acceptable viscosity, when mixed with water in ratios similar to those in the fully hydrated bilayer. The two-phase system of n-hexadecane (C16) as the core surrogate and hydrated DAcPC was used to monitor partitioning of sixteen nonionizable compounds. On the bilogarithmic scale, the C16/DAcPC partition coefficients correlate neither with those in the C16/water and 1-octanol/water systems, nor with their difference, which is frequently used as a parameter of hydrogen bonding for prediction of the bilayer location of the solutes. The C16/DAcPC system provides a satisfactory emulation of the solvation properties of the bilayer regions, as reflected in correct predictions of the bilayer location for those of the studied chemicals, for which this information is available.

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The relationship between peptide structure and transport across epithelial cell monolayers

Cited by 106 publications

References 21 publications

Translocation of Dynorphin Neuropeptides across the Plasma Membrane

Translocation of Dynorphin Neuropeptides across the Plasma Membrane

Differential Interactions of Urocortin/Corticotropin-Releasing Hormone Peptides with the Blood-Brain Barrier

Partitioning of Organic Compounds in Phases Imitating the Headgroup and Core Regions of Phospholipid Bilayers

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