Biomedical subjects

M Rosseneu

Publications and source records attributed to M Rosseneu.

At least 73 records · Page 4Linked to original sources

PubMed1995

Physiological significance of apolipoprotein mutants.

The major plasma lipids, cholesterol, and triglycerides are transported in the blood by different classes of lipoprotein, which can be differentiated from each other by their apoprotein and lipid constituents. Defects in the genes coding for the apolipoprotein components, besides those coding for lipolytic enzymes and cellular receptors, can cause an imbalance in the plasma lipid homeostasis. The physiological significance on lipid metabolism of genetic defects, both rare inborn errors or common genetic variation at these gene loci, are the topics of this review.

Apolipoproteins↗

PubMed1995

Apo(a) phenotypes and Lp(a) concentrations in offspring of men with and without myocardial infarction. The EARS Study. European Atherosclerosis Research Study.

In the European Atherosclerosis Research Study, genetic and environmental markers of risk of premature coronary heart disease were compared in offspring of men with and without myocardial infarction before the age of 55 years. Cases were 682 students with a paternal history of myocardial infarction, and control subjects were 1312 students without such a history. The students were enrolled in 14 universities in five European regions (Finland, Great Britain, and northern, middle, and southern Europe). Lipoprotein(a) [Lp(a)] concentrations were skewed towards lower concentrations in both cases (median, 7.3 mg/dL; 95% confidence interval, 6.3 to 8.1 mg/dL) and control subjects (median, 6.6 mg/dL; 95% confidence interval, 6.1 to 7.2 mg/dL) (P = .37). Significantly more northern European male cases than control subjects had Lp(a) levels exceeding 30 mg/dL (P = .040), but this did not pertain to females (P = .29), and overall, there was no difference between cases (16.5%) and control subjects (15.5%) in the frequency of Lp(a) concentrations above 30 mg/dL (P = .63). As expected, there was a significant (P < .01) inverse relationship between apo(a) molecular size and Lp(a) concentration. In Great Britain there was a significant difference in phenotype distribution between cases and control subjects (P = .035), due mainly to a high frequency of the apo(a) S2 isoform in cases. A similar but statistically insignificant tendency was seen in northern Europeans. In the three other regions, however, the distribution of apo(a) phenotypes among cases and controls was similar, and in the study population overall, the distribution of apo(a) phenotypes did not differ significantly (P = .74) between cases and control subjects.

Adult↗

PubMed1995

Dietary nucleotides enhance plasma lecithin cholesterol acyl transferase activity and apolipoprotein A-IV concentration in preterm newborn infants.

The activity of lecithin cholesterol acyl transferase (LCAT), a key enzyme in lipoprotein metabolism, is low in newborn preterm infants. It has been suggested that a normal gastrointestinal function might be necessary to induce a postnatal increase of LCAT activity because apoproteins A-I and A-IV (apoA-I and apoA-IV) synthesized in considerable amounts in the intestine are known activators of LCAT. Dietary nucleotides have been reported to enhance intestinal growth and maturation; therefore, we hypothesized that nucleotide supplementation to formulas for preterm infants may influence LCAT activity. To investigate this hypothesis, two groups of preterm infants were fed either a nucleotide-free formula or a nucleotide-supplemented formula during the first month of life. The plasma LCAT activity, plasma levels of apoA-I and apoA-IV, plasma cholesteryl esters, and plasma fatty acid composition of cholesteryl esters and phospholipids were then determined. Infants receiving nucleotides had higher LCAT activities and apoA-IV levels than those receiving the nucleotide-free formula for a few weeks. The changes in apoA-IV levels were highly correlated with those of the LCAT activities. However, there were no significant correlations between changes in LCAT activity and plasma cholesteryl esters or phospholipids. These findings indicate that nucleotide supplementation to formulas for preterm infants may improve dietary lipid tolerance by enhancing plasma LCAT activity, probably as a result of an increase in apoA-IV plasma concentrations; they also suggest that nucleotides may enhance apoA-IV synthesis in the intestine during the neonatal period.

Apolipoprotein A-I↗

PubMed1995

Association of synthetic peptide fragments of human apolipoprotein A-I with phospholipids.

The sequences of the plasma apolipoproteins have a high degree of internal homology as they contain several 22-mer internal repeats. These amphipathic helical repeats are considered as the structural and functional units of this class of proteins. We proposed that the 22-mer repeats of the plasma apolipoproteins consist of 17-mer helical segments separated by extended beta-strands comprising five amino acid residues with a proline in the center of this segment. These beta-strand segments help reverse the orientation of the consecutive helices of apoA-I, A-IV, and E in a discoidal apolipoprotein-phospholipid complex. In order to support this hypothesis, we synthesized apoA-I fragments consisting of, respectively, one putative helix (residues 166-183), one helix plus a beta-strand (residues 161-183), and a pair of helices separated by a beta-strand (residues 145-183). The structural and lipid-binding properties of these peptides were investigated by turbidity, fluorescence, binding studies with unilamellar phospholipid vesicles, electron microscopy, and circular dichroism measurements. Our data show that one single putative helical segment or one helical segment plus one extended beta-strand do not form stable complexes with phospholipids. The addition of a second adjacent helix has no influence on the lipid affinity of the apoA-I 145-183 peptide compared to the shorter segments but substantially improves the stability of the complexes. The helical content of the peptide increases upon lipid association as observed with apoA-I. The complexes generated with the apoA-I 145-183 peptide appear as discoidal particles by negative staining electron microscopy, with heterogeneous sizes ranging between 250 and 450 A. The relative orientation of the peptide and the phospholipid is the same as in a DMPC/apoA-I complex as the helices are oriented parallel to the acyl chains of the phospholipid. However, the stability of these complexes is significantly lower than that of the corresponding DMPC/apoA-I complexes. The transition temperature, fluidity, and cooperativity of the phospholipid bilayer are only weakly affected by the association with the apoA-I 145-183 peptide. These data suggest that a pair of helical peptides linked through a beta-strand associates more tightly with lipids and can form discoidal lipid-peptide complexes, than a single helix. A comparison with the properties of native apoA-I suggests, however, that the cooperativity between pairs of helices in native apoA-I further contributes to strengthen the lipid-protein association.

Amino Acids↗

PubMed1994

Identification of specific amphipathic alpha-helical sequence of human apolipoprotein A-IV involved in lecithin:cholesterol acyltransferase activation.

To investigate the structure-function relationship of human apolipoprotein A-IV (apoA-IV), several deletion mutants of this protein were constructed by sequentially removing pairs of 22-residue repeats, potentially having an amphipathic alpha-helical conformation. The mutants, produced as recombinant poly-histidine-tagged apolipoproteins (t-apo) in Escherichia coli, assembled with phosphatidylcholine (i.e. dimyristoylphosphatidylcholine, palmitoyloleoylphosphatidylcholine, or egg lecithin) as did native apoA-IV. Lecithin:cholesterol acyltransferase (LCAT) cofactor function, measured as cholesterol esterification occurring when t-apo-phosphatidylcholine-cholesterol complexes were incubated with purified enzyme, decreased significantly when pairs of repeats between residues 117 and 248 were deleted and most markedly when residues 117-160 were deleted. LCAT cofactor activity decreased by 90 and 75%, respectively, when egg lecithin or palmitoyloleoylphosphatidylcholine was used to form the particles with the delta aa 117-160 mutant. Thus, on the basis of deletion scanning of t-apo, residues 117-160 seem to be involved in the LCAT cofactor function of apoA-IV.

Amino Acid Sequence↗

PubMed1994

Purification and characterization of recombinant human apolipoprotein A-II expressed in Escherichia coli.

We have expressed recombinant human apolipoprotein A-II (apoA-II) in Escherichia coli, as a fusion protein with Schistosoma japonicum glutathione-S-transferase (GST). The GST-AII fusion protein was recovered by affinity chromatography using glutathione as a ligand. After thrombin cleavage and removal of the GST carrier, recombinant apoA-II was obtained in a highly purified form and was exclusively composed of dimeric apoA-II. Kinetics of association to dimyristoylglycerophosphocholine (Myr2GroPCho) vesicles showed that recombinant apoA-II exhibited the same pattern of association as human plasma apoA-II. Electron microscopic analysis of the complexes showed a typical pattern of rouleaux, characteristic of stacked discs, with a diameter similar to that determined by gradient-gel electrophoresis. Circular dichroism measurements showed that the alpha-helical content of both plasma and recombinant apoA-II increased similarly when the proteins associated with Myr2GroPCho vesicles, at the expense of a random-coil structure. Lipid-bound apoA-II consisted of 70-72% alpha helices, suggesting the presence of three 18-residue alpha helices/apoA-II monomer. Cross-linking experiments indicated that Myr2GroPCho complexes contained two molecules dimeric apoA-II/vesicle. Recombinant apoA-II was as efficient as plasma apoA-II in associating with HDL subclasses, and in displacing apoA-I from dipalmitoylglycerophosphocholine/cholesterol/apoA-I complexes, most likely due to its highly ordered secondary structure when associated with Myr2GroPCho vesicles. These findings demonstrate that recombinant apoA-II exhibits the same structural and functional properties as human plasma apoA-II. Thus, the expression system utilized is appropriate to produce mutagenized forms to further structure/function analysis.

Amino Acid Sequence↗

PubMed1994

Structural domain of apolipoprotein A-I involved in its interaction with cells.

Apolipoprotein A-I (apo A-I) is the major protein constituent of high-density lipoprotein (HDL), the lipoprotein fraction which mediates the reverse cholesterol transport. This apolipoprotein plays an important role in the binding of HDL to cells and participates in the efflux of cellular cholesterol. We have recently compared six different genetic variants of apo A-I and found that the apo A-I (Pro 165-->Arg) mutant is defective in promoting cellular cholesterol efflux from murine adipocytes and peritoneal macrophages and we have proposed that this region of apo A-I may be involved in their interaction with cells. To confirm this hypothesis, four monoclonal antibodies (mAbs) specific for apo A-I were used to study the inhibition of the interaction of palmitoyloleoylphosphatidylcholine (POPC): apoA-I complexes with HeLa cells and adipocytes. Among these antibodies, the apo A-I epitope recognized by the A44 mAb lies in the COOH terminal region (amino acid residues 149-186) including the proposed region. The antibodies A05, and A03 react with residues 25-82, 135-140, respectively and the A11 mAb corresponds to a discontinuous epitope at residues 99-105 and 126-132. Our results show clearly that the A44 and A05 mAbs reduce both the binding to HeLa cells and the cholesterol efflux from adipocytes. The inhibition of POPC: apoA-I complexes binding to both cell types is more strictly observed with the Fab fragments of monoclonal antibodies A44 and A05. Partial cotitration curves of these mAbs in a solid phase assay (RIA), indicated partial competition between these two antibodies. We propose a structural model for the POPC: apoA-I complexes where the N-terminal domain of one apo A-I molecule is in close spatial relationship with the C-terminal domain of the adjacent apo A-I molecule. We therefore suggest that the domain around amino acid 165 of apo A-I and which is recognized by mAb A44 (149-186) forms or contains some specific regions which mediate selectively the interaction with the binding site of cells and is involved in the efflux of cellular cholesterol.

Adipocytes↗

PubMed1994

Structure and orientation of apo B-100 peptides into a lipid bilayer.

Peptides corresponding to lipid binding domains of Apo B-100 were synthesized, purified, and incubated with dimyristoylphosphatidylcholine (DMPC) liposomes. The secondary structure of the apo B-100 peptide-lipid complexes was evaluated by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). Those peptides belonging to the hydrophobic "core" domain of apo B-100 when associated with phospholipids were rich in beta sheet structure; a predominant alpha helical conformation was shown to be associated with one peptide located in a surface region of apo B-100. IR dichroic spectra revealed, in the case of the "core" peptides, that the beta sheet component is the only oriented structure with respect to the phospholipid acyl chains. This orientation of the beta sheet was recently found in LDL particles after proteolytic digestion by trypsin (Goormaghtigh, E., Cabiaux, V., De Meutter, J., Rosseneu, M., and Ruysschaert, J. M., 1993, Biochemistry 32, 6104-6110). Altogether, the data suggest that beta sheet, present in a high proportion in the native apo B-100, is probably another protein structure in addition to the amphipathic helix which strongly interacts with the lipid outer layer surrounding the LDL particle.

Apolipoprotein B-100↗

PubMed1994

International Lp(a) standardization.

Two international surveys for Lp(a) measurements were organized from 1989 to 1991. The results of the first survey led to the conclusion that the lack of a common primary standard was the main cause of the large inter-laboratory variation observed. No major effects of techniques or antisera were observed. The same findings were confirmed during the second survey, which was extended to include more samples and a larger number of participants. During the second survey, no consistent effect due to freezing or lyophilization could be demonstrated, although there was a trend towards lower Lp(a) values in lyophilized samples. The inter- and intra-laboratory coefficients of variation did not vary significantly for the different Lp(a) phenotypes, and variability was comparable for lyophilized, liquid and frozen materials. Large intra-assay coefficients of variation were observed during both surveys. Results obtained in different laboratories using the same commercial reagents and standards also showed a large variation. These initial results demonstrate that the lack of a primary standard and poor assay precision are the main factors responsible for the high inter-laboratory variation observed during these surveys.

Analysis of Variance↗

PubMed1994

Enrichment with apolipoprotein E characterizes postprandial TG-rich lipoproteins in patients with non-insulin-dependent diabetes mellitus and coronary artery disease: a preliminary report.

An oral fat-load test was carried out in patients with non-insulin-dependent diabetes mellitus (NIDDM) and angiographically verified coronary artery disease (CAD; group 1, n = 6); in patients with CAD but no diabetes (group 2, n = 6); in patients with NIDDM but no CAD (group 3, n = 4); and in healthy control subjects (group 4, n = 4). Concentrations of apolipoprotein (apo) E, apo C-II, triglyceride (TG), retinyl palmitate, and cholesterol were measured in fasting plasma and in plasma obtained after 2, 4, 6, 9, and 24 h after a meal containing 78 g of fat and 345,000 IU of vitamin A. The same measurements were carried out in the lipoprotein fractions with Svedberg flotation rates Sf 400-1100, 60-400, 20-60 and 12-20, obtained by density gradient ultracentrifugation. The postprandial apo E concentrations were highest in group 1 (NIDDM and CAD) in plasma and in the TG-rich lipoprotein fractions, with significant differences in comparison with the healthy subjects. As shown by apo E to TG ratios, the postprandial lipoproteins were enriched with apo E in the patients with NIDDM and CAD. The largest excesses of apo E in group 1 patients were observed in the atherogenic Sf 12-60 lipoproteins. Across the entire study population, there was a significant inverse correlation between the postprandial apo E responses and the postheparin lipoprotein lipase activity. The results suggest that enrichment of the remnant lipoproteins with apo E may have a role in the increased risk of CAD among patients with NIDDM.

Apolipoprotein C-II↗

PubMed1994

Genetic polymorphism of apolipoprotein A-IV in five different regions of Europe. Relations to plasma lipoproteins and to history of myocardial infarction: the EARS study. European Atherosclerosis Research Study.

As a part of the EARS study we assessed the role of the common apo A-IV polymorphism in determining the hereditary predisposition to cardiovascular disease. The study population consisted of 1261 controls and 629 cases (students whose father had MI before 55 years) from five different European regions. The apo A-IV 1-1 phenotype accounted for 85% of the individuals. One per cent of subjects were homozygous for the apo A-IV2 allele. There was significant regional variation in the apo A-IV allele frequencies from North to South in Europe, with the lowest A-IV2 frequency in Finland. The distribution of the apo A-IV phenotypes was similar in cases and controls, as was the regional variation. The apo A-IV polymorphism did not affect HDL cholesterol. There was no correlation between apo A-IV alleles and the plasma concentration of apo A-IV. The plasma concentration of apo A-IV was lower in females than in males; furthermore, there was a significant difference in apo A-IV concentrations between oral contraceptive users and nonusers: users had the lowest values. As no strongly significant genetic difference could be demonstrated between plasma lipid concentration in cases and controls, and as the apo A-IV polymorphism did not significantly influence plasma lipid concentration, we conclude that the apo A-IV gene is not a major determinant of the risk for MI and/or CHD.

Adolescent↗

PubMed1994

Biomarkers of dietary fat composition in young adults with a parental history of premature coronary heart disease compared with controls. The EARS Study.

The European Atherosclerosis Research Study (EARS) is a study of the biological expression of a paternal history of premature coronary heart disease. The study was carried out in 14 centres in 11 European countries, where the offspring of fathers who suffered a documented myocardial infarction before the age of 55 years (cases) were compared with age- and sex-matched controls. In this paper we describe the measurement of plasma cholesteryl esters as biomarkers for the fatty acid composition of the diet in the cases and controls. No significant differences were found. Cholesteryl palmitate, oleate, linoleate and arachidonate were measured in plasma and correlated with plasma lipids and lipoproteins and with life-style variables including body-mass index, alcohol consumption, tobacco and physical activity. The strongest correlations were observed between cholesteryl esters and triglycerides, which are positively correlated with cholesteryl oleate and negatively with cholesteryl linoleate. Apo B was negatively correlated with cholesteryl linoleate and positively with palmitate. Among the other variables, alcohol was positively correlated with cholesteryl oleate and negatively with linoleate, both in males and in females. Furthermore, there are differences between regions, with the highest percentages of saturated cholesteryl palmitate measured in Finnish students, the highest percentage of cholesteryl linoleate in Belgium and of cholesteryl arachidonate in Southern Europe.

Adolescent↗

PubMed1994

Apolipoprotein E self-association in solution studied by non-radiative energy transfer.

The self-association of human apolipoprotein E (apoE), isolated from plasma very low density lipoproteins, was studied at apoE concentrations less than 0.6 microM by non-radiative energy transfer. ApoE was separately labeled with a fluorescent donor group i.e. dansyl chloride (apoE/D) and with an acceptor i.e. fluorescein isothiocyanate (apoE/F). Mixed apoE/D:apoE/F complexes were prepared either by incubation or the donor- and of the acceptor-labeled apoE or by renaturation during dialysis of the apoE/D:apoE/F mixture pre-denatured by addition of guanidine hydrochloride or by treatment with sodium cholate. The efficiency of energy transfer E at an equimolar ratio of the donor to acceptor and a ratio of 1.9 mol fluorescein/mol protein amounted to 29.2 +/- 2.6% (n = 3). The E value increased linearly with increasing acceptor fraction in the mixture. The state of self-association of apoE as tetramers within this concentration range was confirmed by cross-linking experiments with a water-soluble bifunctional reagent. This approach can be applied to the study of protein-protein interactions in apolipoprotein-phospholipid recombinants.

Apolipoproteins E↗

PubMed1994

Diet and the essential fatty acid status of term infants.

Long-chain polyunsaturated fatty acids with 20 and 22 carbon atoms (LCPs) seem to play an important role during the rapid development of the infant brain in the late fetal and early postnatal period. These LCPs are integral constituents of biological membranes and they are involved in the regulation of functional properties like fluidity, permeability and activity of membrane-bound enzymes. Human milk contains LCPs in an amount of 0.5-3 wt% of total fatty acids, whereas commercially available infant formulae are almost free of them. Recently, several clinical trials, primarily with preterm infants, have reported that the content of LCPs in the blood and a functional parameter like visual acuity correlate with the content of LCPs in the diet. In this clinical trial we studied the effect of different diets on the fatty acid pattern of plasma and erythrocyte lipids of healthy term infants during the first 3 months of life. Breast-fed infants were compared with formula-fed babies who received a commercially available formula without LCPs or a new experimental formula enriched with LCPs that was similar to human milk. The results indicate that the introduction of milk feeding leads to marked differences in the blood lipid composition during the first months of life, independent of the feeding regimen. Secondly, the supplementation of a formula with LCPs seems to result in a blood lipid composition similar to infants fed with human milk. This supports the hypothesis that the newborn term infant has a limited desaturating capacity and depends on an exogenous supply of LCPs during the first months of life.

Arachidonic Acid↗

PubMed1994

Plasma apolipoprotein concentrations in young adults with a parental history of premature coronary heart disease and in control subjects. The EARS Study. European Atherosclerosis Research Study.

The European Atherosclerosis Research Study (EARS) is a multicenter collaborative project within the European community. Its main objective is to study in young individuals the biological expression of a paternal history of premature coronary heart disease and to analyze the relative contribution of genetic and environmental factors to this expression. This study was carried out in 14 centers in 11 European countries, where the offspring of fathers who suffered a documented myocardial infarction before the age of 55 years (cases) were compared with age- and sex-matched control subjects. Plasma apolipoproteins A-I, B, A-II, A-IV, and E and lipoprotein (Lp) A-I lipoparticles were measured in this student population. Comparison of the values between cases and control subjects showed significantly higher apo B levels in cases compared with control subjects, and these differences were homogeneous throughout Europe. Regional differences were observed for apo E levels with an increasing north-south gradient, which was inversely related to that observed for triglycerides. A stepwise regression analysis including the lipid and apolipoprotein variables showed that apo B and triglycerides were the strongest discriminators between offspring of fathers with premature coronary heart disease and control subjects.

Adult↗

PubMed1994

Stimulation with a monoclonal antibody (mAb4E4) of scavenger receptor-mediated uptake of chemically modified low density lipoproteins by THP-1-derived macrophages enhances foam cell generation.

mAb4E4, a murine monoclonal antibody that is specific for acetylated LDL and malondialdehyde-treated LDL, binds specifically to modified LDL present in human atherosclerotic lesions. It is directed against an epitope that is poorly exposed in delipidated and solubilized apolipoprotein B-100 from modified LDL. mAb4E4, as well as its F(ab')2 and Fab fragments, enhanced the uptake of both acetylated LDL and malondialdehyde-treated LDL by THP-1-derived macrophages resulting in a sixfold increase of cytoplasmic cholesteryl ester levels. The increased uptake of modified LDL/mAb4E4 complexes did not occur via the Fc receptor and did not depend on aggregation of modified LDL particles. However, their uptake was inhibited by blocking the scavenger receptors with fucoidin or by downregulation of receptor expression with endotoxins or interferon-gamma, indicating that their uptake is mediated via these receptors. Thus, generation of autoimmune antibodies against modified LDL and subsequent endocytosis of soluble modified LDL/antibody complexes via scavenger receptors may enhance foam cell generation. This mechanism may contribute to the progression of atherosclerotic lesions.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1994

The significance of apolipoprotein E structure to the metabolism of plasma triglyceride-rich lipoproteins.

In this paper we analyse the structural organization of human apolipoprotein E (apoE) at the surface of triglyceride (TG)-rich lipoproteins, in relation to the metabolic pathway of these particles. ApoE acts as a receptor-binding ligand at the surface of chylomicrons and VLDL (very low density lipoproteins). The degree of exposure of apoE at the surface of lipoproteins and its affinity for the receptor both determine the uptake and catabolism of these lipoproteins. ApoE and/or apoB100, the major apolipoprotein constituent of LDL, contribute to the interaction of lipoproteins with five different cellular receptors: 1) the low density lipoprotein (LDL) receptor; 2) the LDL receptor-related protein (LRP); 3) the macrophage receptor for hypertriglyceridemic VLDL; 4) the scavenger receptor; 5) the VLDL receptor. The degree of exposure of apoE at the surface of normo- and hyperlipidemic VLDL can modulate their uptake by the LDL receptor. Normolipidemic VLDL are poorly recognized by the LDL receptor whereas hypertriglyceridemic VLDL are cleared more efficiently through this pathway. On the other hand, the extent of apoE self-association, which is dependent upon the degree of hydrolysis of the TG-rich particles, can control their interaction with the LDL-receptor related protein. The lateral organization of apoE at the surface of TG-rich particles, its interaction with other apoproteins and its extent of self-association might therefore be important factors in the clearance of these lipoproteins. Finally, structural defects of apoE might result in an impaired interaction of apoE-containing lipoproteins with these receptors and lead to the development of atherogenic dyslipidemias.

Animals↗

PubMed1993

Synthetic model peptides for apolipoproteins. I. Design and properties of synthetic model peptides for the amphipathic helices of the plasma apolipoproteins.

Amphipathic helical peptides are the lipid-binding motives of the plasma apolipoproteins, and synthetic peptide analogs have been used to unravel the mechanism of lipid association within this class of proteins. Hydrophobic interactions between the apolar amino acid residues belonging to the hydrophobic face of the amphipathic helices and the lipids are the major driving forces in the peptide-lipid association to form discoidal complexes. Ionic interactions and salt bridge formation between contiguous peptide chains in the complex can, however, contribute to the overall stability of the lipid-protein particle. This was studied by designing peptide analogs to the helical repeats of the apolipoproteins with variable degrees of salt bridge formation between adjacent peptide chains. The most stable conformation for pairs of synthetic peptides was calculated by energy minimisation together with the energy of interaction between peptides. The sequence of the peptides was derived from that of the 18A peptide synthesized by Segrest et al., and the theoretical calculations confirmed that ionic interactions between residues close to each other, along the edge of two adjacent anti-parallel peptides, can significantly contribute towards the stability of a peptide-phospholipid complex.

Amino Acid Sequence↗