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The effect of ionic strength and surface charge density of the lipoplexes formed from the cationic surfactant octadecyltrimethylammonium bromide (OTAB) and the neutral phospholipid 1,2-dioleoyl- -glycero-3-phosphocholine (DOPC) on DNA condensation was studied using fluorescence spectroscopy. The structure of lipoplexes was examined by small- and wide-angle X-ray scattering (SAXS/WAXS). The efficiency of DNA condensation was monitored by relative changes in the intensity of the emission of the fluorescence probe ethidium bromide (EtBr). A high OTAB/DNA charge ratio of 10:1 is required for efficient condensation at all ionic strengths. The increasing mole ratio of OTAB/DOPC supports DNA condensation, while the process is significantly hindered by a high ionic strength. Only ~55% of DNA was found to be condensed by OTAB/DOPC = 1 mol mol complexes in 150 mmol l of NaCl. A condensed fluid lamellar phase (L ) was detected in the DOPC + OTAB + DNA complexes. The SAXS patterns show regular DNA–DNA packing only in complexes prepared in a medium of low ionic strength (<50 mmol l ). Interestingly, free DNA in the supernatant of DOPC + OTAB + DNA complexes was not detected by UV/Vis spectrometry, indicating its trapping in the lipoplexes.

The viral genome of the SARS-CoV-2 coronavirus, the aetiologic agent of COVID-19, encodes structural, non-structural, and accessory proteins. Most of these components undergo rapid genetic variations, though to a lesser extent the essential viral proteases. Consequently, the protease and/or deubiquitinase activities of the cysteine proteases M and PL became attractive targets for the design of antiviral agents. Here, we develop and evaluate new bis(benzylidene)cyclohexanones (BBC) and identify potential antiviral compounds. Three compounds were found to be effective in reducing the SARS-CoV-2 load, with EC values in the low micromolar concentration range. However, these compounds also exhibited inhibitory activity IC against PL at approximately 10-fold higher micromolar concentrations. Although originally developed as PL inhibitors, the comparison between IC and EC of BBC indicates that the mechanism of their antiviral activity is probably not directly related to inhibition of viral cysteine proteases. In conclusion, our study has identified new potential noncytotoxic antiviral compounds suitable for testing and further improvement.

The clinical benefits of using exogenous pulmonary surfactant (EPS) as a carrier of budesonide (BUD), a non-halogenated corticosteroid with a broad anti-inflammatory effect, have been established. Using various experimental techniques (differential scanning calorimetry DSC, small- and wide- angle X-ray scattering SAXS/WAXS, small- angle neutron scattering SANS, fluorescence spectroscopy, dynamic light scattering DLS, and zeta potential), we investigated the effect of BUD on the thermodynamics and structure of the clinically used EPS, Curosurf®. We show that BUD facilitates the Curosurf® phase transition from the gel to the fluid state, resulting in a decrease in the temperature of the main phase transition (Tm) and enthalpy (ΔH). The morphology of the Curosurf® dispersion is maintained for BUD < 10 wt% of the Curosurf® mass; BUD slightly increases the repeat distance d of the fluid lamellar phase in multilamellar vesicles (MLVs) resulting from the thickening of the lipid bilayer. The bilayer thickening (~0.23 nm) was derived from SANS data. The presence of ~2 mmol/L of Ca2+ maintains the effect and structure of the MLVs. The changes in the lateral pressure of the Curosurf® bilayer revealed that the intercalated BUD between the acyl chains of the surfactant’s lipid molecules resides deeper in the hydrophobic region when its content exceeds ~6 wt%. Our studies support the concept of a combined therapy utilising budesonide—enriched Curosurf®.

The influence of cholesterol and β-sitosterol on egg yolk phosphatidylcholine (EYPC) bilayers is compared. Different interactions of these sterols with EYPC bilayers were observed using X-ray diffraction. Cholesterol was miscible with EYPC in the studied concentration range (0–50 mol%), but crystallization of β-sitosterol in EYPC bilayers was observed at X  ≥ 41 mol% as detected by X-ray diffraction. Moreover, the repeat distance ( d ) of the lamellar phase was similar upon addition of the two sterols up to mole fraction 17%, while for X  ≥ 17 mol% it became higher in the presence of β-sitosterol compared to cholesterol. SANS data on suspensions of unilamellar vesicles showed that both cholesterol and β-sitosterol similarly increase the EYPC bilayer thickness. Cholesterol in amounts above 33 mol% decreased the interlamellar water layer thickness, probably due to “stiffening” of the bilayer. This effect was not manifested by β-sitosterol, in particular due to the lower solubility of β-sitosterol in EYPC bilayers. Applying the formalism of partial molecular areas, it is shown that the condensing effect of both sterols on the EYPC area at the lipid–water interface is small, if any. The parameters of ESR spectra of spin labels localized in different regions of the EYPC bilayer did not reveal any differences between the effects of cholesterol and β-sitosterol in the range of full miscibility.

Small-angle neutron scattering data were collected from aqueous dispersions of unilamellar vesicles (ULVs) consisting of mixtures of 1,2-dioleoyl- sn -glycero-3-phosphatidylcholine and a homologous series of N , N -dimethyl- N -alkylamine- N -oxides (C n NO, n  = 12, 14, 16, and 18, where n is the number of carbon atoms in the alkyl chain). A modeling approach was applied to the neutron scattering curves to obtain the bilayer structural parameters. Particularly, the external 2 H 2 O/H 2 O contrast variation technique was carried out on pure dioleoylphosphatidylcholine (DOPC) ULVs to determine the hydrophilic region thickness D h  = 9.8 ± 0.6 Å. Consequently, the hydrocarbon region thickness 2 D C , the lateral bilayer area per one lipid molecule A , and the number of water molecules located in the hydrophilic region per one lipid molecule N W were obtained from single-contrast neutron scattering curves using the previously determined D h . The structural parameters were extracted as functions of r C n NO (the C n NO:DOPC molar ratio) and n . The dependences A ( r C n NO ) provided the partial lateral areas of C n NOs ( A ¯ C n NO ) and DOPC ( A ¯ DOPC ) in bilayers. It was observed that the A ¯ C n NO ’s were constant in the investigated interval of r C n NO and for n  = 12, 14, and 16 equal to 36.6 ± 0.4 Å 2 , while  A ¯ C 18 NO increased to 39.4 ± 0.4 Å 2 . The bilayer hydrocarbon region thickness 2 D C decreased with intercalation of each C n NO. This effect increased with r C n NO and decreased with increasing C n NO alkyl chain length. The intercalation of C18NO changed the 2 D C only slightly. To quantify the effect of C n NO intercalation into DOPC bilayers we fit the 2 D C ( r C n NO ) dependences with weighted linear approximations and acquired their slopes Δ d .

The structures of DMPC and DPPC bilayers in unilamellar liposomes, in the presence of 33.3 mol% cholesterol or the plant sterol β-sitosterol, have been studied by small-angle neutron scattering. The bilayer thickness d L increases in a similar way for both sterols. The repeat distance in multilamellar liposomes, as determined by small-angle X-ray diffraction, is larger in the presence of β-sitosterol than in the presence of cholesterol. We observe that each sterol modifies the interlamellar water layer differently, cholesterol reducing its thickness more efficiently than β-sitosterol, and conclude that cholesterol suppresses bilayer undulations more effectively than β-sitosterol.

We investigate the structure of aggregates formed due to DNA interaction with saturated neutral phosphatidylcholines [dipalmitoylphosphatidylcholine (DPPC) and dimyristoylphosphatidylcholine] in presence of Ca(2+) and Mg(2+) cations using simultaneous synchrotron small- and wide-angle X-ray diffractions. For DPPC:DNA = 3:1 mol/base and in the range of 1-50 mM Ca(2+), the diffractograms show structural heterogeneity of aggregates. We observe the coexistence of two lamellar phases in aggregates prepared at 1 mM Ca(2+): L(x) phase with the DNA strands (of unknown organization) intercalated in water layers between adjacent lipid bilayers and L(DPPC) phase of DPPC bilayers without any divalent cations and DNA strands. Aggregates prepared in the range 2-50 mM Ca(2+) show a condensed gel lamellar phase L (g) (c) with the lipid bilayer periodicity d approximately 8.0 nm, and the DNA-DNA interhelical distance d (DNA) approximately 5.1 nm. The increase of temperature induces the decrease in the intensity and the increase in the width of the DNA related peak. In the fluid state, the condensed lamellar phase L (alpha) (c) gradually converts into L(x) phase. The aggregates do not exhibit rippled P(beta) phase. The thermal behaviour of aggregates was investigated in the range 20-80 degrees C. Applying heating-cooling cycles, the aggregates converted into energetically more favourable structure: a condensed lamellar phase L(c) (or L(x)) is preserved or we observe lateral segregation of the DNA strands and metal cations (L(x) phase) in coexistence with L(PC) phase of pure phospholipids.

Using small angle neutron diffraction and molecular dynamics simulations we studied the interactions between calcium (Ca[2+]) or zinc (Zn[2+]) cations, and oriented gel phase dipalmitoyl-phosphatidylcholine (DPPC) bilayers. For both cations studied at ~1:7 divalent metal ion to lipid molar ratio (Me[2+]:DPPC), bilayer thickness increased. Simulation results helped reveal subtle differences in the effects of the two cations on gel phase membranes.

The study of membranes has become of high importance in the fields of biology, pharmaceutical chemistry and medicine, since much of what happens in a cell or in a virus involves biological membranes. The current book is an excellent introduction to the area, which explains how modern analytical methods can be applied to study biological membranes and membrane proteins and the bioprocesses they are involved to.

The influence of cholesterol and β-sitosterol on egg yolk phosphatidylcholine (EYPC) bilayers is compared. Different interactions of these sterols with EYPC bilayers were observed using X-ray diffraction. Cholesterol was miscible with EYPC in the studied concentration range (0-50 mol%), but crystallization of β-sitosterol in EYPC bilayers was observed at X ≥ 41 mol% as detected by X-ray diffraction. Moreover, the repeat distance (d) of the lamellar phase was similar upon addition of the two sterols up to mole fraction 17%, while for X ≥ 17 mol% it became higher in the presence of β-sitosterol compared to cholesterol. SANS data on suspensions of unilamellar vesicles showed that both cholesterol and β-sitosterol similarly increase the EYPC bilayer thickness. Cholesterol in amounts above 33 mol% decreased the interlamellar water layer thickness, probably due to \"stiffening\" of the bilayer. This effect was not manifested by β-sitosterol, in particular due to the lower solubility of β-sitosterol in EYPC bilayers. Applying the formalism of partial molecular areas, it is shown that the condensing effect of both sterols on the EYPC area at the lipid-water interface is small, if any. The parameters of ESR spectra of spin labels localized in different regions of the EYPC bilayer did not reveal any differences between the effects of cholesterol and β-sitosterol in the range of full miscibility.[PUBLICATION ABSTRACT]