Person:
Cañadas Benito, Olga

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First Name
Olga
Last Name
Cañadas Benito
URI
https://hdl.handle.net/20.500.14352/74363
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Ciencias Biológicas
Department
Bioquímica y Biología Molecular
Area
Bioquímica y Biología Molecular
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2006 - 20072
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Author: Johnson, Mark E. × Item Type: Publication × Subject: 612.2 ×

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Now showing 1 - 2 of 2
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    Physical properties and surface activity of surfactant-like membranes containing the cationic and hydrophobic peptide KL4
    (The FEBS Journal, 2006) Sáenz, Alejandra; Cañadas Benito, Olga; Bagatolli, Luís A.; Johnson, Mark E.; Casals Carro, María Cristina
    Surfactant-like membranes containing the 21-residue peptide KLLLLKLLLLKLLLLKLLLLK (KL4), have been clinically tested as a therapeutic agent for respiratory distress syndrome in premature infants. The aims of this study were to investigate the interactions between the KL4 peptide and lipid bilayers, and the role of both the lipid composition and KL4 structure on the surface adsorption activity of KL4-containing membranes. We used bilayers of three-component systems [1,2-dipalmitoyl-phosphatidylcholine ⁄ 1-palmitoyl-2-oleoyl-phosphatidylglycerol ⁄ palmitic acid (DPPC⁄POPG⁄ PA) and DPPC⁄ 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) ⁄PA] and binary lipid mixtures of DPPC⁄POPG and DPPC⁄PA to examine the specific interaction of KL4 with POPG and PA. We found that, at low peptide concentrations, KL4 adopted a predominantly a-helical secondary structure in POPG- or POPC-containing membranes, and a b-sheet structure in DPPC⁄PA vesicles. As the concentration of the peptide increased, KL4 interconverted to a b-sheet structure in DPPC⁄POPG⁄PA or DPPC⁄POPC⁄PA vesicles. Ca2+ favored a«b interconversion. This conformational flexibility of KL4 did not influence the surface adsorption activity of KL4-containing vesicles. KL4 showed a concentration-dependent ordering effect on POPG- and POPC-containing membranes, which could be linked to its surface activity. In addition, we found that the physical state of the membrane had a critical role in the surface adsorption process. Our results indicate that the most rapid surface adsorption takes place with vesicles showing well-defined solid ⁄ fluid phase co-existence at temperatures below their gel to fluid phase transition temperature, such as those of DPPC⁄POPG⁄PA and DPPC⁄POPC⁄ PA. In contrast, more fluid (DPPC⁄POPG) or excessively rigid (DPPC⁄ PA) KL4-containing membranes fail in their ability to adsorb rapidly onto and spread at the air–water interface.
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    Effect of surfactant protein A on the physical properties and surface activity of KL4-surfactant
    (Biophysical Journal, 2007) Sáenz, Alejandra; Cañadas Benito, Olga; Bagatolli, Luís A.; Sánchez Barbero, Fernando; Johnson, Mark E.; Casals Carro, María Cristina
    SP-A, the major protein component of pulmonary surfactant, is absent in exogenous surfactants currently used in clinical practice. However, it is thought that therapeutic properties of natural surfactants improve after enrichment with SP-A. The objective of this study was to determine SP-A effects on physical properties and surface activity of a new synthetic lung surfactant based on a cationic and hydrophobic 21-residue peptide KLLLLKLLLLKLLLLKLLLLK, KL4. We have analyzed the interaction of SP-A with liposomes consisting of DPPC/POPG/PA (28:9:5.6, w/w/w) with and without 0.57 mol % KL4 peptide. We found that SP-A had a concentration-dependent effect on the surface activity of KL4-DPPC/POPG/PA membranes but not on that of an animal-derived LES. The surface activity of KL4-surfactant significantly improved after enrichment with 2.5–5 wt % SP-A. However, it worsened at SP-A concentrations $10 wt %. This was due to the fluidizing effect of supraphysiological SP-A concentrations on KL4-DPPC/POPG/PA membranes as determined by fluorescence anisotropy measurements, calorimetric studies, and confocal fluorescence microscopy of GUVs. High SP-A concentrations caused disappearance of the solid/fluid phase coexistence of KL4-surfactant, suggesting that phase coexistence might be important for the surface adsorption process.