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1.
Synthesis of a novel lipopeptide with α-melanocyte-stimulating hormone peptide ligand and its effect on liposome stability 总被引:1,自引:0,他引:1
Yoshikatsu Ogawa Hidehiko Kawahara Nobuhiro Yagi Masato Kodaka Takenori Tomohiro Tomoko Okada Takeo Konakahara Hiroaki Okuno 《Lipids》1999,34(4):387-394
Introduction of liposomes into target cells is important for drug delivery systems. For this purpose, the surface of the liposome
is equipped with ligand peptides, which may bind to specific receptors on the cell membrane. An artificial novel lipopeptide
(MSH-C4A2) containing the α-melanocyte-stimulating hormone (α-MSH) sequence and two long alkyl chains was designed and synthesized,
and the liposome, composed of egg phosphatidylcholine (EPC) and MSH-C4A2, was prepared. The stability of the liposome was
estimated by measuring calcein leakage from the liposome inner phase. The stability of the liposome decreased upon addition
of MSH-A4C2, which seemed to be attributable to the amphiphilic property of the peptide moiety (α-MSH) of MSH-A2C4. The stability
was, however, recovered fairly well upon addition of cholesterol (Ch) or phosphatidylglycerol (PG). It was concluded therefore
that the ternary system, MSH-C4A2/Ch/EPC or MSH-C4A2/PG/EPC, is suitable for preparing the functional liposome. 相似文献
2.
Liposomes made from a natural marine lipid extract and containing a high polyunsaturated n−3 fatty lipid ratio were envisaged
as oral route vectors and a potential α-tocopherol supplement. The behavior of vesicles obtained by simple filtration and
of giant vesicles prepared by electroformation was investigated in gastrointestinal-like conditions. The influence of α-tocopherol
incorporation into liposomes was studied on both physical and chemical membrane stability. Propanal, as an oxidation product
of n−3 polyunsaturated fatty acids, was quantified by static headspace gas chromatography when α-tocopherol incorporation
into liposome ratios ranged from 0.01 to 12 mol%. Best oxidative stability was obtained for liposomes that contained 5 mol%
α-tocopherol. Compared to the other formulas, propanal formation was reduced, and time of the oxidation induction phase was
longer. Moreover, α-tocopherol induced both liposome structural modifications, evidenced by turbidity, and phospholipid chemical
hydrolysis, quantified as the amount of lysophospholipids. This physicochemical liposome instability was even more pronounced
in acid storage conditions, i.e., α-tocopherol incorporation into liposome membranes accelerated the structural rearrangements
and increased the rate of phospholipid hydrolysis. In particular, giant vesicles incubated at pH 1.5 underwent complex irreversible
shape transformations including invaginations. In parallel, the absorption rate of α-tocopherol was measured in lymph-cannulated
rats when α-tocopherol was administrated, as liposome suspension or added to sardine oil, through a gastrostomy tube. α-Tocopherol
recovery in lymph was increased by almost threefold, following liposome administration. This may be related to phospholipids
that should favor α-tocopherol solubilization and to liposome instability in the case of a high amount of α-tocopherol in
the membranes. A need to correlate results obtained from in vitro liposome behavior with in vivo lipid absorption was demonstrated by this study. 相似文献
3.
Waterhouse JE Harbottle RP Keller M Kostarelos K Coutelle C Jorgensen MR Miller AD 《Chembiochem : a European journal of chemical biology》2005,6(7):1212-1223
One of the main problems facing gene therapy is the ability to target the delivery of DNA to specific cells of choice. Recently, we developed a synthetic nonviral vector platform system known as LMD (liposome:mu:DNA) that was designed for further modular upgrading with tool-kits of chemical components. First-generation LMD systems were prepared from DC-Chol/DOPE cationic liposomes (DC-Chol=3beta-[N-(N',N'-dimethylaminoethane)carbamoyl] cholesterol, DOPE=dioleoyl-L-alpha-phosphatidylethanolamine), mu peptide from the adenovirus core and plasmid DNA (pDNA). Here we report attempts to realise peptide-targeted gene delivery that build upon the LMD platform. Our strategy was to prepare novel lipopeptides with a lipid moiety designed to insert into the outer lipid bilayer of LMD particles whilst simultaneously presenting a peptide moiety for cell-surface receptor binding. One main functional peptide sequence was selected (PLAEIDGIELA; tenascin peptide sequence) known to target alpha(9)beta(1)-integrin proteins predominant on upper-airway epithelial cells. This sequence was investigated along with a corresponding control sequence. The syntheses of two classes (A and B) of lipopeptides are reported; the syntheses of class A lipopeptides requires a modification of Mitsunobu chemistry that could be of general utility to facilitate Mitsunobu reactions in other diverse systems. "Targeted" LMD and LD transfections with class A or B lipopeptides exhibit nonspecific peptide enhancements (up to one order of magnitude) over nonlipopeptide control transfections but few specific effects. Specific targeting effects can be seen if the overall LMD or LD particle cationic charge is lowered, but nonspecific effects are never eliminated. Whilst promising, these data now highlight the need for in vivo data and even a new modular, aqueous chemistry for the controlled adaptation of LMD particles in buffer in order for successful peptide-targeted, synthetic, nonviral gene delivery to be realised. 相似文献
4.
Novel RGD lipopeptides for the targeting of liposomes to integrin-expressing endothelial and melanoma cells 总被引:4,自引:0,他引:4
Hölig P Bach M Völkel T Nahde T Hoffmann S Müller R Kontermann RE 《Protein engineering, design & selection : PEDS》2004,17(5):433-441
RGD peptides targeting alphav-integrins are promising ligands for the generation of vascular targeting agents. We isolated from phage display RGD motif libraries novel high-affinity cyclic RGD peptides by selection on either endothelial or melanoma cells. Although the starting sequences contained only two cysteine residues flanking the RGD motif, several of the isolated peptides possessed four cysteine residues. A high-affinity peptide (RGD10) constrained by only one disulfide bond was used to generate novel lipopeptides composed of a lipid anchor, a short flexible spacer and the peptide ligand conjugated to the spacer end. Incorporation of RGD10 lipopeptides into liposomes resulted in specific and efficient binding of the liposomes to integrin-expressing cells. In vivo experiments applying doxorubicin-loaded RGD10 liposomes in a C26 colon carcinoma mouse model demonstrated improved efficacy compared with free doxorubicin and untargeted liposomes. 相似文献
5.
Monitoring monohydroperoxides in docosahexaenoic acid using high-performance liquid chromatography 总被引:2,自引:0,他引:2
The oxidation of free DHA has been investigated with respect to monohydroperoxides and polyhydroperoxides, which were analyzed
with a novel HPLC method. The temperature and physical system, i.e., bulk and liposome, were varied. We have also studied
the effects of antioxidants such as α-tocopherol, ascorbic acid, and juice from sea buckthorn on DHA. The HPLC method, which
was performed isocratically, eluted eight peaks, each containing one or two isomers of monohydroperoxy-DHA. This method showed
that the double bond farthest from the carboxyl group was easily oxidized, as shown by the rapid increase in the amount of
C20-monohydroperoxy-DHA, which always provided the largest contribution to the total amount of monohydroperoxides. The monohydroperoxy-DHA
containing the hydroperoxy group located on the double bond nearest the carboxyl group also was shown to incease considerably
during an increase in the total amount of monohydroperoxides. This demonstrates that the double bonds located nearest and
farthest from the carboxyl group were the most prome to hydroperoxide formation. DHA was more stable when stored in liposomes
than as bulk. Addition of α-tocopherol to the DHA-containing liposomes reduced the oxidation of these double bonds. The antioxidant
effect of α-tocopherol was prolonged when combined with ascorbic acid, since α-tocopherol was regenerated. 相似文献
6.
Oxidation ofR,R,R-α-tocopherol (vitamin E; TH) by peroxyl radicals generated from the azo initiator azobis(2,4-dimethylvaleronitrile) in acetonitrile, hexane, or in phospholipid liposomes yields 8a-(alkyldioxy)tocopherone adducts,
8a-(hydroxy)tocopherone, and their hydrolysis product α-tocopherolquinone TH oxidation also yields 4a,5-epoxy- and 7,8-epoxy-8a-(hydroperoxy)tocopherones
and their respective hydrolysis products 2,3-epoxy-α-tocopherolquinone and 5,6-epoxy-α-tocopherolquinone. Previous work indicates
that the distribution of TH oxidation products varies with reaction environment. We investigated the dependence of antioxidant
stoichiometry on TH oxidation product distribution for reactions in hexane, acetonitrile, and in phosphatidylcholine liposomes.
Yields of 8a-substituted tocopherones were highest in hexane and lowest in phosphatidylcholine liposomes. In contrast, yields
of epoxide products were highest in the liposome system and lowest in hexane. Yields of α-tocopherolquinone were similar in
all three systems. Antioxidant stoichiometry, measured by the inhibited autoxidation method, was approximately 2.0 peroxyl
radicals trapped per TH consumed in acetonitrile and in liposomes. In hexane, a slightly larger stoichiometric factor of approximately
2.5 was measured. This may, in part, reflect the generation of more reactive alkoxyl radicals in hexane. The reaction environment
thus markedly affects the balance between competing TH oxidation pathways but produces comparatively little effect on antioxidant
stoichiometry. These results imply that competing reaction pathways contribute similarly to the antioxidant chemistry of TH. 相似文献
7.
Lipid peroxidation in unilamellar liposomes of known cholesterol-phospholipid composition was monitored under conditions of
autoxidation or as induced by a superoxide radical generating system, γ-irradiation or cumene hydroperoxide. Formation of
cholesterol oxidation products was indexed to the level of lipid peroxidation. The major cholesterol oxidation products identified
were 7-keto-cholesterol, isomeric cholesterol 5,6-epoxides, isomeric 7-hydroperoxides and isomeric 3,7-cholestane diols. Other
commonly encountered products included 3,5-cholestadiene-7-one and cholestane-3β,5α,6β-triol. Superoxide-dependent peroxidation
required iron and produced a gradual increase in 7-keto-cholesterol and cholesterol epoxides. Cholesterol oxidation was greatest
in liposomes containing high proportions of unsaturated phospholipid to cholesterol (4∶1 molar ratio), intermediate with low
phospholipid to cholesterol ratios (2∶1) and least in liposomes prepared with dipalmitoylphosphatidylcholine and cholesterol.
This relationship held regardless of the oxidizing conditions used. Cumene hydroperoxide-dependent lipid peroxidation and/or
more prolonge oxidations with other oxidizing systems yielded a variety of products where cholesterol-5β,6β-epoxide, 7-ketocholesterol
and the 7-hydroperoxides were most consistently elevated. Oxyradical initiation of lipid peroxidation produced a pattern of
cholesterol oxidation products distinguishable from the pattern derived by cumene hydroperoxide-dependent peroxidation. Our
findings indicate that cholesterol autoxidation in biological membranes is modeled by the peroxide-induced oxidation of liposomes
bearing unsaturated fatty acids and suggest that a number of cholesterol oxidation products are derived from peroxide-dependent
propagation reactions occurring in biomembranes. 相似文献
8.
The 1O2 quenching rate constants (k
Q
) of α-tocopherol (α-Toc) and carotenoids such as β-carotene, astaxanthin, canthaxanthin, and lycopene in liposomes were determined
in light of the localization of their active sites in membranes and the micropolarity of the membrane regions, and compared
with those in ethanol solution. The activities of α-Toc and carotenoids in inhibiting 1O2-dependent lipid peroxidation (reciprocal of the concentration required for 50% inhibition of lipid peroxidation: [IC50]−1) were also measured in liposomes and ethanol solution and compared with their k
Q
values. The k
Q
and [IC50]−1 values were also compared in two photosensitizing systems containing Rose bengal (RB) and pyrenedodecanoic acid (PDA), respectively,
which generate 1O2 at different sites in membranes. The k
Q
values of α-Toc were 2.9×108M−1s−1 in ethanol solution and 1.4×107 M−1s−1 (RB system) or 2.5×106 M−1s−1 (PDA system) in liposomes. The relative [IC50]−1 value of α-Toc in liposomes was also five times higher in the RB system than in the PDA-system. In consideration of the local
concentration of the OH-group of α-Toc in membranes, the k
Q
value of α-Toc in liposomes was recalculated as 3.3×106 M−1s−1 in both the RB and PDA systems. The k
Q
values of all the carotenoids tested in two photosensitizing systems were almost the same. The k
Q
value of α-Toc in liposomes was 88 times less than in ethanol solution, but those of carotenoids in liposomes were 600–1200
times less than those in ethanol solution. The [IC50]−1 value of α-Toc in liposomes was 19 times less than that in ethanol solution, whereas those of carotenoids in liposomes were
60–170 times less those in ethanol solution. There were no great differences (less than twice) in the k
q
and [IC50]−1 values of any carotenoids. The k
Q
values of all carotenoids were 40–80 times higher than that of α-Toc in ethanol solution but only six times higher that of
α-Toc in liposomes. The [IC50]−1 values of carotenoid were also higher than that of α-Toc in ethanol solution than in liposomes, and these correlated well
with the k
Q
values. 相似文献
9.
Van Bambeke F Kerkhofs A Schanck A Remacle C Sonveaux E Tulkens PM Mingeot-Leclercq MP 《Lipids》2000,35(2):213-223
We examined changes in membrane properties upon acidification of dioleoylphosphatidylethanolamine/cholesterylhemisuccinate
liposomes and evaluated their potential to deliver entrapped tracers in cultured macrophages. Membrane permeability was determined
by the release of entrapped calcein or hydroxypyrene-1,3,6-trisulfonic acid (HPTS)-p-xylene-bis-pyridinium bromide (DPX); membrane fusion, by measuring the change in size of the liposomes and the dequenching
of octadecylrhodamine-B fluorescence; and change in lipid organization, by31P nuclear magnetic resonance spectroscopy. Measurement of cell-associated fluorescence and confocal microscopy examination
were made on cells incubated with liposomes loaded with HPTS or HPTS-DPX. The biophysical studies showed (i) a lipid reorganization
from bilayer to hexagonal phase progressing from pH 8.0 to 5.0, (ii) a membrane permeabilization for pH<6.5, (iii) an increase
in the mean diameter of liposomes for pH<6.0, and (iv) a mixing of liposome membranes for pH<5.7. The cellular studies showed
(i) an uptake of the liposomes that were brought from pH 7.5–7.0 to 6.5–6.0 and (ii) a release of ∼15% of the endocytosed
marker associated with its partial release from the vesicles (diffuse localization). We conclude that the permeabilization
and fusion of pH-sensitive liposomes occur as a consequence of a progressive lipid reorganization upon acidification. These
changes may develop intracellular after phagocytosis and allow for the release of the liposome content in endosomes associated
with a redistribution in the cytosol. 相似文献
10.
A novel phospholipid containing a chromanol structure at its polar head group was synthesized from egg yolk phosphatidylcholine
and 2,5,7,8-tetramethyl-6-hydroxy-2-(hydroxyethyl)chroman by transphosphatidylation catalyzed by phospholipase D fromStreptomyces lydicus. The structure of the product synthesized was shown by spectral analysis to be 1,2-diacyl-sn-glycero-3-phospho-2′-hydroxyethyl-2′ 5′,7′,8′-tetramethyl-6′-hydroxychroman. The phosphatidylchromanol (PCh) showed antioxidant
activity against radical chain oxidation of methyl linoleate in solution in a manner similar to that ofd-α-tocopherol (α-Toc) and 2,2,5,7,8-pentamethyl-6-chromanol. However, PCh was less effective as a chain-breaking antioxidant
than was α-Toc when unilamellar egg yolk phosphatidylcholine liposomes were exposed to either a water-soluble or a lipid-soluble
radical initiator. It is likely that the phospholipid nature of PCh affects the location and the mobility of the chromanol
moiety in the membrane bilayer resulting in a decrease in antioxidant activity. On the other hand, the antioxidant activity
of PCh was little different from that of α-Toc in unilamellar liposomes when exposed to a lipid-soluble radical initiator
in the presence of ascorbic acid. It appears that PCh in phospholipid bilayers can be regenerated by ascorbic acid in aqueous
phase as can be α-Toc. The new phospholipid, phosphatidylchromanol, should prove useful as a chain-breaking antioxidant in
phospholipid membranes. 相似文献
11.
Marine lipid-based liposomes increase <Emphasis Type="Italic">in vivo</Emphasis> FA bioavailability 总被引:1,自引:0,他引:1
Liposomes made from an extract of natural marine lipids and containing a high n-3 PUFA lipid ratio were envisaged as oral
route vectors for FA supplements in order to increase PUFA bioavailability. The absorption of FA in thoracic lymph duct-cannulated
rats, after intragastric feeding of dietary fats in the form of liposomes or fish oil, was compared. Lipid and FA analyses
were also performed on feces. Five mole percent α-tocopherol was added to fish oil and incorporated into the liposome membrane.
The influence of α-tocopherol on FA lymph recovery was also investigated. In vivo, FA absorption in rats was favored by liposomes (98±1%) compared to fish oil (73±6%). In the same way, the DHA proportion
in lymph was higher after liposome ingestion (78%) than after fish oil ingestion (47%). However, phospholipid (PL) concentration
in lymph was not affected by the kind of dietary fat ingested, suggesting a PL regulation due to de novo TAG synthesis. The influence of the intramolecular distribution of n-3 PUFA in dietary lipids (TAG and PL) on the intramolecular
FA distribution in TAG of chylomicrons was also investigated. The results obtained showed that the distribution of n-3 PUFA
esterified on the sn-2 of chylomicron TAG depended on the lipid source administered. All these results correlated, at least partly, with in vitro liposome behavior under conditions that mimic those of the gastrointestinal tract. As a whole, this study pointed out that
marine PL may constitute an attractive material for the development of liposomes as oral PUFA supplements. 相似文献
12.
Masakazu Yamaoka Maria Josette H. Carrillo Toro Nakahara Kanki Komiyama 《Journal of the American Oil Chemists' Society》1991,68(2):114-118
Antioxidative activity of tocotrienol (Toc3) was studied in the oxidation of dilinoleoylphosphatidylcholine (DLPC) liposomes.
The objective was to measure the differences in the antioxidative activities betweenα-Toc3 andα-tocopherol (α-Toc), and betweenγ-Toc3 andγ-Toc. When each antioxidant was added to the already prepared DLPC liposome solution, the antioxidative activity of Toc3 was
larger than that of Toc. However, when incorporated into the liposomal membrane, the antioxidative activities of Toc3 and
Toc were the same and were intermediate between those of the added Toc3 and Toc.
When added to the liposome solution, the consumption of Toc3 during the induction period was larger than that of Toc. When
incorporated into the liposomal membrane, the consumptions of Toc3 and Toc were the same and were intermediate between those
of the added Toc3 and Toc.
These results suggest that the reactions of Toc3 and Toc with phospholipid peroxide within the membrane are inhibited to a
different degree depending on the dosing manner of Toc3 and Toc. Namely, the degree of inhibition decreases in the following
order: Toc(added)> Toc(incorporated)= Toc3(incorporated)> Toc3(added). 相似文献
13.
Cholesterol was used as an in situ probe for studying mechanisms of lipid peroxidation in isolated erythrocyte membranes subjected
to different prooxidant conditions. The membranes were labeled with [14C]cholesterol by exchange with prelabeled unilamellar liposomes and photosensitized with hematoporphyrin derivative. Irradiation
with a dose of blue light resulted in thiobarbituric acid-detectable lipid peroxidation that was increased markedly by subsequent
dark incubation with 0.5–1.0 mM ascorbate (AH−). Ascorbate-stimulated lipid peroxidation was inhibited by EDTA, desferrioxamine (DOX) and butylated hydroxytoluene (BHT),
suggesting that the process is free radical in nature and catalyzed by membrane-bound iron. Thin layer chromatography and
radiometric scanning of extracted lipids from photooxidized membranes revealed that the major oxidation product of cholesterol
was the 5α-hydroperoxide (5α-OOH), a singlet oxygen adduct. Post-irradiation treatment with AH−/Fe(III) resulted in an almost-total disappearance of 5α-OOH and the preponderance of free radical oxidation products, e.g.
7-ketocholesterol, the epimeric 7α-/7β-hydroperoxides (7α-/7β-OOH) and their respective alcohols (7α-/7β-OH). EDTA, DOX and
BHT inhibited the formation of these products, while catalase and superoxide dismutase had no effect. These results are consistent
with a mechanism involving 1-electron reduction of photogenerated hydroperoxides to oxyl radical, which trigger bursts of
free radical lipid peroxidation. Though generated in this system, partially reduced oxygen species, viz. superoxide, hydrogen
peroxide and hydroxyl radical, appear to be relatively unimportant in the autoxidation process.
Presented at the symposium “Free Radicals Antioxidants, Skin Cancer and Related Diseases” at the 78th AOCS Annual Meeting
in New Orleans, LA, May 1987. 相似文献
14.
James M. Trazaskos Wayne D. Bowen Gary J. Fisher Jeffrey T. Billheimer James L. Gaylor 《Lipids》1982,17(3):250-256
Our principal goal is the complete resolution and reconstitution of the microsomal enzymes of cholesterol biosynthesis. Elucidation
of the enzymology has been achieved primarily through dissection of the membrane-bound, 19-step multienzymic process. This
report describes the dissection approach through both interruption of specific steps and reconstitution of enzymes that catalyze
oxidation of the 14α-methyl group. In earlier work, 4-demethylation was resolved into 3 component reactions catalyzed by:
4-methyl sterol oxidase (NAD[P] H- and O2-dependnet); steroid 4α-carboxylic acid decarboxylase (NAD-dependent); and 3-ketosteroid reductase (NADPH-dependent). The
3-ketosteroid reductase and decarboxylase have been solubilized with Lubrol WX and deoxycholate, respectively, and characterized.
The 4-methyl sterol oxidase (cytochrome b5-dependent) recently has been solubilized with Renex 690. This study represents successful elucidation of a microsomal enzyme
sequence by interruption of the central 10-step segment of the multienzymic formation of cholesterol from lanosterol. The
initial C-32 oxidative reaction of 14α-methyl group elimination is catalyzed by a from of cytochrome P-450 that is induced
by isosafrole. The induced cytochrome P-450 has been solubilized with Emulgen 913 and purified to homogeneity (17 nmol of
cytochrome/mg protein). 24,25-Dihydrolanosterol is oxidized by combination of cytochrome P-450 reductase, hematin, NADPH,
glutathione, and the purified, isosafrole-induced cytochrome in an artificial liposome. Oxidation product identification is
underway. This study represents successful elucidation of a microsomal multienzymic sequence by solubilization and reconstitution
of a segment of the pathway. The remaining enzymes under study are the Δ8→Δ7 isomerase and 3 NADPH-dependent double bond reductases that catalyze reduction of: Δ7, Δ14- Δ24-sterol double bonds. Purification of these nonoxygenrequiring enzymes is in progress. Resolution of the enzymes has demonstrated
unequivocally that cholesterol synthesis via this pathway could not have appeared biologically until membranes containedboth the cytochrome P-450- and cytochrome b5-electron transport enzymes. Chemically, all enzymic attacks in the formation of cholesterol from lanosterol appear to be
initiated on the α-face of the relatively planar steroids. Thus, considerable genetic pressure must have been needed for the
stereospecific clearing of the steroidal α-face to form the mature membrane component, cholesterol. 相似文献
15.
A persistent problem in measurement of cholesterol 7α-hydroxylase (7α-OHase) activity by isotope incorporation has been solubilization
of cholesterol substrate. Solubilization with Tween 20, for example, resulted in a 75% reduction in 7α-OHase activity after
a 60 min incubation of substrate with microsomes. Incorporation of cholesterol substrate into small, unilamellar phospholipid
vesicles (liposomes) prevented this effect, resulting in a 50% increase in activity over the same 60 min incubation at optimal
concentrations. Using cholesterol in liposomes as substrate, standard assay conditions were determined to be: preparation
of liposomes with 180 μM cholesterol substrate and 0.5 mg phospholipid/assay; incubation of these liposomes with 0.5 mg microsomal
protein at 37 C for 60 min; addition of a NADPH generating system to start the reaction, and incubation at 37 C for 30 min
before stopping the reaction and determining the amount of 7α-hydroxycholesterol formed. In addition to preventing the detergent-related
inhibition of the enzyme, liposome-solubilized substrate also reduced the variation among replicates from a coefficient of
45% with Tween 20 to 4.2% with phospholipid. This method provides a sensitive and reliable alternative to methods which require
more sophisticated equipment and allows total control of substrate concentration in a form readily accessible to the enzyme.
This work was reported in part at the American Society of Biological Chemists Meeting, St. Louis, Missouri, June 1984. 相似文献
16.
Lins L.; Flore C.; Chapelle L.; Talmud P.J.; Thomas A.; Brasseur R. 《Protein engineering, design & selection : PEDS》2002,15(6):513-520
The lipid-interacting properties of the N-terminal domain ofhuman apolipoprotein C-III (apo C-III) were investigated. Bymolecular modeling, we predicted that the 620 fragmentof apo C-III is obliquely orientated at the lipid/water interfaceowing to an asymmetric distribution of the hydrophobic residueswhen helical. This is characteristic of `tilted peptides' originallydiscovered in viral fusion proteins and later in various proteinsincluding some involved in lipoprotein metabolism. Since mosttilted peptides were shown to induce liposome fusion in vitro,the fusogenic capacity of the 620 fragment of apo C-IIIwas tested on unilamellar liposomes and compared with the wellcharacterized SIV fusion peptide. Mutants were designed by molecularmodeling to assess the role of the hydrophobicity gradient inthe fusion. FTIR spectroscopy confirmed the predominantly helicalconformation of the peptides in TFE solution and also in lipidpeptidecomplexes. Lipid-mixing experiments showed that the apo C-III(620) peptide is able to increase the fluorescence ofa lipophilic fluorescent probe. The vesicle fusion was confirmedby core-mixing and leakage assays. The hydrophobicity gradientplays a key role in the fusion process because the mutant withno hydrophobic asymmetry but the same mean hydrophobicity asthe wild type does not induce significant lipid fusion. Theapo C-III (620) fragment is, however, less fusogenicthan the SIV peptide, in agreement with their respective meanhydrophobicity. Since lipid fusion should not be the physiologicalfunction of the N-terminal domain of apo CIII, we suggest thatits peculiar distribution of hydrophobic residues is importantfor the lipid-binding properties of apo C-III and should beinvolved in apolipoprotein and lipid exchanges crucial for triglyceridemetabolism. 相似文献
17.
Three novel cationic liposomes were prepared from commercial soybean lecithin (neutral liposome) and stearylamine (cationic liposome) as a catalyst or accelerating agent for the alkaline hydrolysis of polyester fabric. The formation of 1:1, 1:6 and 1:12 cationic liposomes was confirmed by transmission electron microscopy, nitrogen content and Fourier Transform‐infrared spectroscopy. Factors affecting the alkaline hydrolysis performance of polyester fabric in the presence and absence of cationic liposomes were investigated. Size measurements of the three cationic liposomes showed that the vesicle size was 27.88 nm for the 1:1 cationic liposome, 15.57 nm for 1:6 and 10 nm for 1:12, in comparison with 50 nm for neutral liposome. The results showed that alkaline hydrolysis in the presence of cationic liposomes improves the hydrophilicity and dyeability of polyester fabric and creates more carboxylic groups on the fabric. The silky polyester fabric was characterised by scanning electron microscopy, tensile strength, elongation at break, crease recovery angle and surface roughness to prove the success of the cationic liposomes as accelerating agents in the alkaline hydrolysis process. The results also indicate that the colour strength of hydrolysed polyester fabric in the presence of cationic liposomes dyed with disperse dye was slightly higher than that obtained in the absence of cationic liposomes and with unhydrolysed fabric. Furthermore, the fastness properties of hydrolysed polyester in the absence and presence of cationic liposomes do not vary. 相似文献
18.
Monika Wojciechowska Joanna Miszkiewicz Joanna Trylska 《International journal of molecular sciences》2020,21(24)
Many peptides interact with biological membranes, but elucidating these interactions is challenging because cellular membranes are complex and peptides are structurally flexible. To contribute to understanding how the membrane-active peptides behave near the membranes, we investigated peptide structural changes in different lipid surroundings. We focused on two antimicrobial peptides, anoplin and W-MreB1–9, and one cell-penetrating peptide, (KFF)3K. Firstly, by using circular dichroism spectroscopy, we determined the secondary structures of these peptides when interacting with micelles, liposomes, E. coli lipopolysaccharides, and live E. coli bacteria. The peptides were disordered in the buffer, but anoplin and W-MreB1–9 displayed lipid-induced helicity. Yet, structural changes of the peptide depended on the composition and concentration of the membranes. Secondly, we quantified the destructive activity of peptides against liposomes by monitoring the release of a fluorescent dye (calcein) from the liposomes treated with peptides. We observed that only for anoplin and W-MreB1–9 calcein leakage from liposomes depended on the peptide concentration. Thirdly, bacterial growth inhibition assays showed that peptide conformational changes, evoked by the lipid environments, do not directly correlate with the antimicrobial activity of the peptides. However, understanding the relation between peptide structural properties, mechanisms of membrane disruption, and their biological activities can guide the design of membrane-active peptides. 相似文献
19.
Jinlong Yang Jie Xu Ning Wen Yanan Qu Fei Qi Xiaoqing Xi 《Journal of the American Ceramic Society》2013,96(1):62-67
Thermo‐sensitive liposomes were prepared using reverse phase evaporation method using natural lipid egg phosphatidylcholine (EPC) and cholesterol (CH). Inorganic salts containing high valence counterions (HVCI) are encapsulated by the liposomes. The phase transition temperature of the liposome is at 38°C with 50 wt% addition of cholesterol. The encapsulation rate of liposomes reaches 85% for high valence anion (SO42?) and 55% for high valence cation (Ca2+). The liposomes are introduced into ceramic colloidal forming and dispersed in the suspension for identical charge with alumina particles at room temperature. The release of HCVI from the liposomes can coagulate the alumina suspension after heating at 38°C for 3 h, but the de‐moldable time is ~ 6–7 h. Dense ceramic products with relative density of above 98% and uniform microstructure can be prepared by this method without burnout process. 相似文献
20.
Summary Giant hybrid liposomes of polymerizable lipid and cholesterol were prepared by the hydration method and were polymerized by UV irradiation. The obtained giant liposomes were freeze-dried and washed with chloroform to skeletonize the frame structure of the polymerized membrane. The skeletonized liposomes were directly confirmed by scanning electron microscopy. The single-layered and fully spherical liposome frame were easily confirmed by the stereo-pair of the obtained micrographs. 相似文献