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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Ye, Guofeng Gupta, Anju DeLuca, Robert Parang, Keykavous Bothun, Geoffrey D. |
| Description | Country affiliation: United States Author Affiliation: Ye G ( Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA.) |
| Abstract | The effects of a series of low molecular weight water-soluble cationic linear peptide analogs (LPAs, <1000 MW) with increasing hydrophobic/hydrophilic balance on lipid bilayer phase behavior and permeability were examined using liposomes composed of zwitterionic dipalmitoylphosphatidylcholine (DPPC) and mixed zwitterionic/anionic DPPC/dipalmitoylphosphatidylglycerol (DPPG) lipid bilayers. LPAs were synthesized using a previously reported alkyl linkage strategy as Arg-C(n)-Arg-C(n)-Lys, where C(n) represents the saturated alkyl linkage separating the cationic residues (n=4, 7, or 11) (Ye et al., 2007 [1]). Differential scanning calorimetry results show that the cationic LPAs bound to and disrupted DPPC and, to a greater extent, DPPC/DPPG phase behavior. When added to preformed unilamellar liposomes, the LPAs led to significant structural changes based on cryogenic transmission electron microscopy (cryo-TEM). Coupling cryo-TEM with carboxyfluorescein leakage studies indicate that the LPAs induced permeabilization through bilayer expansion, which caused membrane thinning. The effects were inconsistent with increasing LPA hydrophobicity, which suggests that a cooperative effect between electrostatic binding and hydrophobic insertion determined the location of LPAs within the bilayer and their membrane activity. Our results for LPA-induced membrane disruption correlate with previous breast cancer cell uptake studies that showed minimal LPA-C(4) uptake, but high LPA-C(11) uptake through a non-endocytic mechanism. |
| File Format | HTM / HTML |
| ISSN | 09277765 |
| Issue Number | 1 |
| Volume Number | 76 |
| e-ISSN | 18734367 |
| Journal | Colloids and Surfaces B: Biointerfaces |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2010-03-01 |
| Publisher Place | Netherlands |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Chemistry Arginine Chemistry Lipid Bilayers Liposomes Peptides 1,2-dipalmitoylphosphatidylcholine Calorimetry, Differential Scanning Microscopy, Electron, Scanning Molecular Structure Phosphatidylglycerols Solubility Thermodynamics Water Journal Article Research Support, Non-u.s. Gov't Research Support, U.s. Gov't, Non-p.h.s. |
| Content Type | Text |
| Resource Type | Article |
| Subject | Colloid and Surface Chemistry Medicine Physical and Theoretical Chemistry Surfaces and Interfaces Biotechnology |
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