Anionic Proteins Research Articles

Tuning of protein-surfactant interaction to modify the resultant structure.

Small-angle neutron scattering and dynamic light scattering studies have been carried out to examine the interaction of bovine serum albumin (BSA) protein with different surfactants under varying solution conditions. We show that the interaction of anionic BSA protein (pH7) with surfactant and the resultant structure are strongly modified by the charge head group of the surfactant, ionic strength of the solution, and mixed surfactants. The protein-surfactant interaction is maximum when two components are oppositely charged, followed by components being similarly charged through the site-specific binding, and no interaction in the case of a nonionic surfactant. This interaction of protein with ionic surfactants is characterized by the fractal structure representing a bead-necklace structure of micellelike clusters adsorbed along the unfolded protein chain. The interaction is enhanced with ionic strength only in the case of site-specific binding of an anionic surfactant with an anionic protein, whereas it is almost unchanged for other complexes of cationic and nonionic surfactants with anionic proteins. Interestingly, the interaction of BSA protein with ionic surfactants is significantly suppressed in the presence of nonionic surfactant. These results with mixed surfactants thus can be used to fold back the unfolded protein as well as to prevent surfactant-induced protein unfolding. For different solution conditions, the results are interpreted in terms of a change in fractal dimension, the overall size of the protein-surfactant complex, and the number of micelles attached to the protein. The interplay of electrostatic and hydrophobic interactions is found to govern the resultant structure of complexes.

Phase separation and composition of coacervates of lactoferrin and caseins

The bovine milk casein proteins (αs-casein (ACN), β-casein (BCN) and κ-casein (KCN)) form complexes with lactoferrin (LF), an anionic protein also present in bovine milk that has an important bacteriostatic function especially in infant food. LF and each casein form complexes at near neutral pH, which is in between the respective pI's (≈8.3 and ≈ 4.6). The stoichiometry of the complexes is determined by the net charge of the proteins. Optimum complexation occurs at charge neutrality and is characterized by a maximum in turbidity. Mixing LF with each casein at a ratio where charge neutrality is obtained leads to a new complex coacervate phase. The kinetics of complex formation for LF/BCN and LF/KCN is rapid and appears to occur through a nucleation and coalescence process. However, the kinetics of complex formation between LF and ACN is much slower and therefore a nucleation and growth process is proposed, based on model calculations of the turbidity. The composition of the complexes is the same as the experimental mixing ratio if mixing ratio leads to a neutral complex. On standing and light centrifugation a complex-coacervate phase is formed, which is a viscous liquid.

Abstract 310: Oxidized LDL-binding Cationic Peptides and Proteins in Inflammation and Atherosclerosis: Novel Insights

Background: Apolipoprotein A1 and apolipoprotein E mimetic peptides have attracted attention due to their ability to reduce atherosclerosis and exhibit antioxidant, anti-inflammatory, and hypolipidemic properties. We previously reported that the non-lipoprotein-related Lys-Arg-rich cationic peptides have anti-inflammatory properties both in vitro and in vivo. In this study, we have determined whether ApoB100 of low density lipoprotein (N-LDL), which is Lys-Arg rich, has similar properties. Methods: 5F-mimetic peptide of ApoA1, LL27 derived from the anti-microbial peptide CAMP, and a human glycodelin derived peptide, were commercially synthesized. N-LDL was prepared and used. The ability of these peptides and protein to neutralize charges of modified lipoproteins, as well as attenuate macrophage uptake and inflammation, were analyzed. Oxidized LDL (Ox-LDL) was pretreated with increasing concentrations of peptides and N-LDL to evaluate charge neutralizing properties of the peptides as well as that of the protein (ApoB100). RAW cells were incubated with LPS or Ox-LDL pretreated with and without peptides and N-LDL. RNA was isolated from treated cells and real time PCR was performed using mouse IL-1α and IL-6 primers. Results: Cationic peptides as well as ApoB100 protein of N-LDL decomposed the peroxide content of 13-HPODE. Incubation of Ox-LDL and Ac-LDL with the peptides as well as ApoB100 resulted in charge neutralization as noted by agarose gel electrophoresis. Pre-incubation of the peptides and N-LDL with modified lipoproteins reduced the uptake of the latter by macrophages and foam cell formation as detected by Oil-Red O staining. Reduced inflammation was observed in the presence of N-LDL as compared to LPS/Ox-LDL. Conclusions: Based on these studies, we postulate that cationic peptides and protein might have properties that would a) affect events that are unrelated to lipid lowering, b) might play an additional role in immune competent cells, including macrophages, and c) might interact with other biologically important anionic molecules, including lipids and proteins. We also predict that lysine-rich cationic peptides and proteins could have therapeutic potential in reducing CVD/atherosclerosis-associated inflammation.

Chitosan nanoparticles for the linear release of model cationic Peptide.

The present study is focused on the development of a model drug delivery system (DDS) based on Chitosan (CS) nanoparticles using Renin substrate I (RSI) as model agent. RSI shares the main chemical-physical features of several biologically active antimicrobial peptides (AMPs). AMPs have a great therapeutic potential that is hampered by their lability in the biological fluids and as such they are perfect candidates for DDS. The development studies of quality DDS loaded with AMPs would require highly sensitive and specific quantification assays. The use of RSI allowed for the fine-tuning and optimization of the formulation parameters to promote the hydrophobic interactions between CS and the cationic peptide, favour the loading of the active ingredient and enhance the release properties of the carrier. RSI was encapsulated in chitosan NPs by mean of ionic gelation and a chromogenic enzymatic essay was carried out for the release kinetics evaluation. The developed formulations displayed almost 100% of encapsulation efficacy, low burst percentages, and a linear release of the model peptide. A release model was created showing a direct dependence on both the amount of RSI and NPs radius. Although CS has always been formulated with negatively charged active agents (e.g. oligonucleotides or anionic proteins), the use of ionotropic gelation in presence of a small cationic active agent promoted the formation of "core-shell" NPs. The described model, with tuneable linear release rates, appears eligible for further exploitation such as the loading of therapeutically active AMPs.

Impact of pH on the structure and function of neural cadherin.

Neural (N-) cadherin is a transmembrane protein within adherens junctions that mediates cell-cell adhesion. It has 5 modular extracellular domains (EC1-EC5) that bind 3 calcium ions between each of the modules. Calcium binding is required for dimerization. N-Cadherin is involved in diverse processes including tissue morphogenesis, excitatory synapse formation and dynamics, and metastasis of cancer. During neurotransmission and tumorigenesis, fluctuations in extracellular pH occur, causing tissue acidosis with associated physiological consequences. Studies reported here aim to determine the effect of pH on the dimerization properties of a truncated construct of N-cadherin containing EC1-EC2. Since N-cadherin is an anionic protein, we hypothesized that acidification of solution would cause an increase in stability of the apo protein, a decrease in the calcium-binding affinity, and a concomitant decrease in the formation of adhesive dimer. The stability of the apo monomer was increased and the calcium-binding affinity was decreased at reduced pH, consistent with our hypothesis. Surprisingly, analytical SEC studies showed an increase in calcium-induced dimerization as solution pH decreased from 7.4 to 5.0. Salt-dependent dimerization studies indicated that electrostatic repulsion attenuates dimerization affinity. These results point to a possible electrostatic mechanism for moderating dimerization affinity of the Type I cadherin family. Extrapolating these results to cell adhesion in vivo leads to the assertion that decreased pH promotes adhesion by N-cadherin, thereby stabilizing synaptic junctions.

Multiple EPS interactions involved in the cohesion and structure of aerobic granules

This study aims to clarify the biochemical nature and interactions of Extracellular Polymeric Substances (EPS) involved in the structure and cohesive properties of aerobic granules. Granules were incubated with selective hydrolytic enzymes or with chemicals and the resistance of digested granules to shear stress was evaluated. After α-amylase digestion, the hydrodynamic stress released macro-particles (>315μm) while soluble molecules (<1.5μm) and micro-particles (1.5–315μm) where mainly recovered after savinase and EDTA treatments. These data show that α (1–4) glucans and proteins are key polymers for granule cohesion and that divalent cationic bridging is a major aggregative mechanism.On the basis of these experiments and microscopy observations, a model is proposed for the spatial organization of EPS in the granular structure, in which α glucans are arranged in a capsular layer surrounding bacterial clusters while anionic proteins constitute the intercellular cement that may reinforce cohesion inside the bacterial clusters.

Équilibre acidobasique : acidoses et alcaloses métaboliques

Acid-base homeostasis ensured by the kidneys, which maintain the equilibrium between proton generation by cellular metabolism and proton excretion in urine. This requirement is lifesaving because of the protons’ ability to bind to anionic proteins in the extracellular space, modifying their structure and functions. The kidneys also regenerate bicarbonates. The kidney is not the sole organ in charge of maintaining blood pH in a very narrow range; lungs are also involved since they allow a large amount of volatile acid generated by cellular respiration to be eliminated.

Complex coacervates of lactotransferrin and β-lactoglobulin

HypothesisOppositely charged proteins should interact and form complex coacervates or precipitates at the correct mixing ratios and under defined pH conditions. ExperimentsThe cationic protein lactotransferrin (LF) was mixed with the anionic protein β-lactoglobulin (B-Lg) at a range of pH and mixing ratios. Complexation was monitored through turbidity and zeta potential measurements. FindingsComplexation between LF and B-Lg did occur and complex coacervates were formed. This behaviour for globular proteins is rare. The charge ratio’s of LF:B-Lg varies with pH due to changing (de) protonation of the proteins. Nevertheless we found that the complexes have a constant stoichiometry LF:B-Lg=1:3 at all pH’s, due to charge regularization. At the turbidity maximum the zeta potential of complexes is close to zero, indicating charge neutrality; this is required when the complexes form a new concentrated liquid phase, as this must be electrically neutral. Complexes were formed in pH region 5–7.3. On addition of salt (NaCl) complexation is diminished and disappears at a salt concentration of about 100mMol. The coacervate phase has a very viscous consistency. If we consider the proteins as colloidal particles then the formed complex coacervate phase may have a structure that resembles a molten salt comparable to, for example, AlCl3.

Protein cytoplasmic delivery using polyampholyte nanoparticles and freeze concentration

A protein delivery method using freeze concentration was presented with a variety of polyampholyte nanocarriers. In order to develop protein nanocarriers, hydrophobically modified polyampholytes were synthesized by the succinylation of ε-poly-l-lysine with dodecyl succinic anhydride and succinic anhydride. The self-assembled polyampholyte aggregated form nanoparticles through intermolecular hydrophobic and electrostatic interactions when dissolved in aqueous media. The cationic and anionic nanoparticles were easily prepared by changing the succinylation ratio. Anionic or cationic proteins were adsorbed on/into the nanoparticles depending on their surface charges. The protein-loaded nanoparticles were stable for at least 7 d. When L929 cells were frozen with the protein-loaded nanoparticles in the presence of a cryoprotectant, the adsorption of the protein-loaded nanoparticles was enhanced and can be explained by the freeze concentration mechanism. After thawing, proteins were internalized into cells via endocytosis. This was the first report that showed that the efficacy of protein delivery was successfully enhanced by the freeze concentration method. This method could be useful for in vitro cytoplasmic protein or peptide delivery to various cells for immunotherapy or phenotype transformations.

Mixed Layers of β-Lactoglobulin and SDS at Air–Water Interfaces with Tunable Intermolecular Interactions

Mixtures of β-lactoglobulin (BLG) and sodium dodecyl sulfate (SDS) were studied at pH 3.8 and 6.7 under equilibrium conditions. At these pH conditions, BLG carries either a positive or a negative net charge, respectively, which enables tunable electrostatic interactions between anionic SDS surfactants and BLG proteins. For pH 3.8, vibrational sum-frequency generation (SFG) and ellipsometry indicate strong BLG-SDS complex formation at air-water interfaces that is caused by attractive electrostatic interactions. The latter complexes are already formed in the bulk solution which was confirmed by a thermodynamic study of BLG-SDS mixtures using isothermal titration calorimetry (ITC). For acidic conditions we determine from our ITC data an exothermal binding enthalpy of -40 kJ mol(-1). Increasing SDS/BLG molar ratios above 10 leads to a surface excess of SDS and thus to a charge reversal from a positive net charge with BLG as the dominating surface adsorbed species to a negatively charged layer with SDS as the dominating surface species. The latter is evidenced by a pronounced minimum in SFG intensities that is also accompanied by a phase change of O-H stretching bands due to a reorientation of H2O within the local electric field. This phase change which occurs at SDS/BLG molar ratio between 1 and 10 causes a polarity change in SFG intensities from BLG aromatic C-H stretching vibrations. Conclusions from SFG spectra are corroborated by ellipsometry which shows a dramatic increase in layer thicknesses at molar ratios where a charge reversal occurs. The formation of interfacial multilayers comprising SDS-BLG complexes is, thus, caused by cancellation of electrostatic interactions which leads to agglomeration at the interface. In contrast to pH 3.8, behavior of BLG-SDS mixtures at pH 6.7 is different due to repulsive electrostatic interactions between SDS and BLG which lead to a significantly reduced binding enthalpy of -17 kJ mol(-1). Finally, it has to be mentioned that SFG spectra show a coexistence of BLG and SDS molecules at the interface for BLG-SDS molar ratios > 2.

Characterization of the mucilage isolated from the edible fronds of bird's nest fern (Asplenium australasicum)

With the increasing attentions in exploiting natural additives for food industry, the mucilage isolated from the young fronds of Asplenium australasicum (J. Sm.) Hook under diverse extraction conditions was investigated for their physicochemical properties. It was observed that the yields of the mucilage were generally raised with increasing citric acid concentration, extraction temperature and time. Chemical analysis revealed that the mucilage was composed mainly of anionic polysaccharides and proteins (4.7–20.7%), depending on the extraction conditions. Furthermore, in comparison with some commercial food hydrocolloids reported in the literatures, A. australasicum mucilage showed significant surface activity, as evidenced by a pronounced reduction (about 29–36%) on the surface tension of water and excellent emulsion stability in a model oil-in-water type emulsion. The surface tension of A. australasicum mucilage solution decreased with increasing mucilage concentration to a certain point (0.075–0.1%), but remained fairly constant as the mucilage concentration was further increased up to 0.5%. Moreover, the emulsifying activity of A. australasicum mucilage was pH and oil/water volume ratio dependent. These results suggest that the acid-extracted mucilage from the young fronds of A. australasicum is a potential natural thickener and emulsification stabilizer.

Topical Delivery of Avastin to the Posterior Segment of the Eye In Vivo Using Annexin A5‐associated Liposomes

Effective delivery to the retina is presently one of the most challenging areas in drug development in ophthalmology, due to anatomical barriers preventing entry of therapeutic substances. Intraocular injection is presently the only route of administration for large protein therapeutics, including the anti-Vascular Endothelial Growth Factors Lucentis (ranibizumab) and Avastin (bevacizumab). Anti-VEGFs have revolutionised the management of age-related macular degeneration and have increasing indications for use as sight-saving therapies in diabetes and retinal vascular disease. Considerable resources have been allocated to develop non-invasive ocular drug delivery systems. It has been suggested that the anionic phospholipid binding protein annexin A5, may have a role in drug delivery. In the present study we demonstrate, using a combination of in vitro and in vivo assays, that the presence of annexin A5 can significantly enhance uptake and transcytosis of liposomal drug carrier systems across corneal epithelial barriers. This system is employed to deliver physiologically significant concentrations of Avastin to the posterior of the rat eye (127 ng/g) and rabbit retina (18 ng/g) after topical application. Our observations provide evidence to suggest annexin A5 mediated endocytosis can enhance the delivery of associated lipidic drug delivery vehicles across biological barriers, which may have therapeutic implications.

Protein Crowder Charge and Protein Stability

Macromolecular crowding effects arise from steric repulsions and weak, nonspecific, chemical interactions. Steric repulsions stabilize globular proteins, but the effect of chemical interactions depends on their nature. Repulsive interactions such as those between similarly charged species should reinforce the effect of steric repulsions, increasing the equilibrium thermodynamic stability of a test protein. Attractive chemical interactions, on the other hand, counteract the effect of hard-core repulsions, decreasing stability. We tested these ideas by using the anionic proteins from Escherichia coli as crowding agents and assessing the stability of the anionic test protein chymotrypsin inhibitor 2 at pH 7.0. The anionic protein crowders destabilize the test protein despite the similarity of their net charges. Thus, weak, nonspecific, attractive interactions between proteins can overcome the charge-charge repulsion and counterbalance the stabilizing effect of steric repulsion.

Diacylglycerol kinase γ is a novel anionic phospholipid binding protein with a selective binding preference

There are ten isozymes of diacylglycerol kinase (DGK), and they regulate diverse patho-physiological functions. Here, we investigated the lipid-binding properties of DGK isozymes using protein–lipid overlay and liposome-binding assays. DGKγ showed a strong binding activity compared with other DGK isozymes for phosphatidic acid (PA) among the various glycerophospholipids tested. However, DGKγ failed to interact with DG and lyso-PA. Moreover, the isozyme was capable of binding to ceramide-1-phosphate but not to ceramide or sphingosine-1-phosphate. The isozyme bound more strongly to PA containing unsaturated fatty acid than to PA having only saturated fatty acid. An analysis using a series of deletion mutants of DGKγ revealed that the N-terminal region, which contains a recoverin homology domain and EF-hand motifs, is responsible for the PA binding activity of DGKγ. Taken together, these results indicate that DGKγ is an anionic phospholipid binding protein that preferably interacts with a small highly charged head group that is very close to the glycerol or sphingosine backbone.

In Situ Evaluation of Nanoparticle–Protein Interactions by Dynamic Magnetic Susceptibility Measurements

The use of dynamic magnetic susceptibility measurements is reported to study nanoparticle–protein interactions in situ. The technique consists of measuring the rotational diffusivity of thermally blocked magnetic nanoparticles (MNPs) in protein solutions. To illustrate the technique, the effect of nanoparticle zeta potential in carboxymethyl‐dextran‐coated MNPs and their interaction with model anionic and cationic proteins, such as bovine serum albumin (BSA), immunoglobulin G (IgG), fibrinogen (FIBR), apo‐transferrin (TRANS), lysozyme (LYZ), and histone (HIS), in a range of protein concentrations is studied. Experiments indicate that interactions between the negatively charged particles and the negatively charged proteins BSA, IgG, FIBR, and TRANS are negligible. However, positively charged proteins LYZ and HIS readily absorb onto the nanoparticles, as evidenced by an increase in size and eventual aggregation of the particles. Onset of this effect seems to happen at a lower concentration of HIS compared with LYZ. The technique could be applied to other particle surface coatings and to particles in complex protein mixtures, such as whole blood and serum, allowing systematic in situ studies of nanoparticle–protein interactions.

Molecular mechanisms involved in plant adaptation to low K+ availability

Potassium is a major inorganic constituent of the living cell and the most abundant cation in the cytosol. It plays a role in various functions at the cell level, such as electrical neutralization of anionic charges, protein synthesis, long- and short-term control of membrane polarization, and regulation of the osmotic potential. Through the latter function, K(+) is involved at the whole-plant level in osmotically driven functions such as cell movements, regulation of stomatal aperture, or phloem transport. Thus, plant growth and development require that large amounts of K(+) are taken up from the soil and translocated to the various organs. In most ecosystems, however, soil K(+) availability is low and fluctuating, so plants have developed strategies to take up K(+) more efficiently and preserve vital functions and growth when K(+) availability is becoming limited. These strategies include increased capacity for high-affinity K(+) uptake from the soil, K(+) redistribution between the cytosolic and vacuolar pools, ensuring cytosolic homeostasis, and modification of root system development and architecture. Our knowledge about the mechanisms and signalling cascades involved in these different adaptive responses has been rapidly growing during the last decade, revealing a highly complex network of interacting processes. This review is focused on the different physiological responses induced by K(+) deprivation, their underlying molecular events, and the present knowledge and hypotheses regarding the mechanisms responsible for K(+) sensing and signalling.

The Materials Science of Pathological Crystals

Aberrant crystallization within the human body can lead to several disease states, although traditionally the pathogenesis of such diseases has not been studied from a materials science perspective. A fundamental understanding of the nucleation and growth, sometimes followed by aggregation and adhesion of crystals to tissue, is essential for the elucidation of the mechanisms directing the pathogenesis of these diseases. The quest for a greater understanding of these in vivo events has prompted the use of innovative experimental approaches aimed at understanding them at a microscopic level, often under conditions thought to emulate a physiological environment. Real-time, in situ atomic force microscopy (AFM) has been used to elucidate the effect of urinary substituents on calcium-containing crystals that aggregate to form kidney stones, demonstrating the role of anionic proteins, synthetic polymers and small molecules on crystal growth regulation. Through an understanding of the structure of l-cystine crystals, which produce a rare and severe form of kidney stones, intermolecular interactions necessary for the growth of these crystals were identified and molecular inhibitors were designed that bind stereospecifically to actively growing crystal faces, thereby suppressing growth. X-ray diffraction techniques have been used to investigate the nucleation of cholesterol crystals within lipid membranes, providing insight into the formation of atherosclerotic plaques and crystals that can aggregate to form gallstones. The discovery of the crystal structure of hemozoin, which results from the crystallization of free heme within the digestive vacuole of the prevalent malaria parasite Plasmodium falciparum, combined with grazing angle X-ray diffraction and other methods, has informed on the mode of action of common antimalarial drugs, providing guidance for the development of new therapies that can overcome the increasing resistance of the parasite to current drugs. The role of materials science in the study of pathological conditions is expected to become increasingly significant as crystal growth theory, solid-state chemistry, and materials characterization methods are applied to a greater breadth of disorders, ranging from crystalline amyloid proteins associated with neurodegenerative diseases to unwanted in vivo crystallization of administered pharmacological compounds.

Thromboelastography (TEG) Cups and Pins with Different PECVD Coatings: Effect on the Coagulation Cascade in Platelet‐poor Blood Plasma

Thromboelastography uses cups and pins made of Cyrolite® plastic to analyze the rate of fibrin clot formation in blood samples. In this study, TEG cups and pins were modified by 4 distinct coating types using plasma‐enhanced chemical vapor deposition (PECVD): carboxylated, amine‐rich, hydrophobic, SiO2, and analyzed for surface chemistry and wettability. We tested the hypothesis that the coagulation kinetics of recalcified citrated blood plasma is controlled by surface chemistry, in the absence of clot activator. Only carboxylated surfaces became negatively charged upon wetting, and accelerated clot formation in a highly reproducible manner, whereas Cyrolite® and the other coatings had delayed and unpredictable clotting times. These data are consistent with a model whereby carboxylated surfaces selectively adsorb and activate factor XII while repelling other more abundant anionic blood proteins, resulting in reproducible clot kinetics.

Zwitterionic Phenyl Layers: Finally, Stable, Anti-Biofouling Coatings that Do Not Passivate Electrodes

Organic coatings on electrodes that limit biofouling by proteins but are of sufficiently low impedance to still allow Faradaic electrochemistry to proceed at the underlying electrode are described for the first time. These organic coatings formed using simple aryl diazonium salts present a zwitterionic surface and exhibit good electrochemical stability. The layers represent a low impedance alternative to the oligo (ethylene glycol) (OEG)-based anti-biofouling coatings and are expected to find applications in electrochemical biosensors and implantable electrodes. Two different zwitterionic layers grafted to glassy carbon surfaces are presented and compared to a number of better-known surfaces, including OEG-based phenyl-layer-grafted glassy carbon surfaces and OEG alkanethiol SAMs coated on gold, to allow the performance of these new layers to be compared to the body of work on other anti-biofouling surfaces. The results suggest that phenyl-based zwitterionic coatings are as effective as the OEG SAMs at resisting the nonspecific adsorption of bovine serum albumin and cytochrome c, as representative anionic and cationic proteins at physiological pH, whereas the impedance of the zwitterionic phenyl layers are two orders of magnitude lower than OEG SAMs.

Abstract 454: Cationic Peptides Neutralize Ox-LDL and Acetyl LDL Negative Charge and Prevent Their Uptake by Macrophages

Background Apoprotein (Apo A1) and apoprotein E mimetic peptides are known to reduce atherosclerosis. Antioxidant, anti-inflammatory, and hypolipidemic properties have been suggested to contribute to the anti-atherosclerotic effects. In this study, we tested whether three distinct and unrelated cationic peptides would inhibit the oxidation of lipoproteins and whether they would counteract and neutralize the negatively charged modified lipoproteins and inhibit their uptake by macrophages. Methods 5F-mimetic peptide of apoA1, LL27 derived from the anti-microbial peptide CAMP, and a human glycodelin derived peptide were commercially synthesized. The number of positively charged amino acid residues (K+R) and negatively charged residues (D+E) were 4/4, 7/4, 6/2 respectively. Their abilities to reduce lipid peroxides (LOOH), inhibit the oxidation low density lipoprotein (LDL) and high density lipoprotein (HDL), interact with modified lipoproteins, and to inhibit macrophage uptake of modified LDL were measured. Results Cationic peptides decomposed the peroxide content of 13-HPODE and inhibited the oxidation of LDL and HDL by copper in a lysine dependent manner. Incubation of Ox-LDL and Ac-LDL with the peptides resulted in charge neutralization as noted by agarose gel electrophoresis. Pre-incubation of the peptides with modified lipoproteins reduced the uptake of the latter by macrophages and foam cell formation as detected by Oil-Red O staining. Conclusions Based on these studies, we postulate that cationic peptides may have properties that may affect a) events that are unrelated to lipid lowering, b) may play additional role in immune competent cells, including macrophages, and c) may interact with other biologically important anionic molecules, including lipids and proteins. These results also suggest there may be other cationic proteins that may influence the atherogenic processes.