Hydrophobic Laminin-Related Peptides: Synthesis and Surface Properties

The synthesis of hydrophobic peptide derivatives related to the laminin sequence [YIGSR(NH(2))] is described. Hydrophobicity is achieved by the attachment of decanoic, myristic, or stearic acids to the amino terminal end of the peptide. Moreover, a cholesterol residue was also introduced as succinimidoyl-cholesteryl moiety at the same position. These peptidic compounds are designed to be inserted into lipid bilayers to prepare, what can be considered as, immunoliposomes to target these vesicles to tumor cells. Physicochemical aspects related to their surface activity, insertion into lipid layers, spreadibility, formation of aggregates, and haemolytic activity have been studied as a previous step in the selection of the most convenient derivative. The results obtained indicate that these peptide derivatives show a high tendency to form aggregates in aqueous media, this fact reducing their interaction with lipid mono- and bilayers. The most suitable derivatives for interacting with liposomes are myristoyl and decanoyl. Copyright 2001 Academic Press.     

Progress toward a peptidomimetic of laminin-derived pentapeptide YIGSR: synthesis of the unique tricyclic core structure

The peptide sequence YIGSR, a segment of the basement membrane matrix glycoprotein laminin, has been identified as a key component in tumor cell invasion. Guided by extensive NMR work and de novo design algorithms, a nonpeptide mimetic of this pentapeptide was identified as a lead candidate for synthesis. The target displays the key amino acid side chains from a novel tricyclic scaffold. The first synthesis of this unique scaffold is completed in 11 steps and 7% overall yield.     

Physicochemical study of laminin-related peptides

Four peptide analogues related to the active sequence YIGSR of laminin have been synthesised. The synthesis and chemical characterisation of the peptides are described. Physicochemical properties of these peptides such as surface activity, spreadability, monolayer formation, as well as their interaction with lipid monolayers and bilayers, have been studied by using Langmuir-Blodgett films and liposomes as membrane models. In spite of their good water solubility, these peptides are able to form stable monolayers at the air/water interface and to insert into lipid monolayers. The interaction with bilayers is soft; they are not able to induce the leakage of entrapped CF nor to modify the microviscosity of bilayers in general. Thus in these models electrostatic forces apparently do not play an important role, as we expected previously according to the electrical charge of bilayers, markers and peptides.     

Covalent attachment of TAT peptides and thiolated alkyl molecules on GaAs surfaces

Four TAT peptide fragments were used to functionalize GaAs surfaces by adsorption from solution. In addition, two well-studied alkylthiols, mercaptohexadecanoic acid (MHA) and 1-octadecanethiol (ODT) were utilized as references to understand the structure of the TAT peptide monolayer on GaAs. The different sequences of TAT peptides were employed in recognition experiments where a synthetic RNA sequence was tested to verify the specific interaction with the TAT peptide. The modified GaAs surfaces were characterized by atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared reflection absorption spectroscopy (FT-IRRAS). AFM studies were used to compare the surface roughness before and after functionalization. XPS allowed us to characterize the chemical composition of the GaAs surface and conclude that the monolayers composed of different sequences of peptides have similar surface chemistries. Finally, FT-IRRAS experiments enabled us to deduce that the TAT peptide monolayers have a fairly ordered and densely packed alkyl chain structure. The recognition experiments showed preferred interaction of the RNA sequence toward peptides with high arginine content.     

Cell adhesion properties on photochemically functionalized diamond

The biocompatibility of diamond was investigated with a view toward correlating surface chemistry and topography with cellular adhesion and growth. The adhesion properties of normal human dermal fibroblast (NHDF) cells on microcrystalline and ultrananocrystalline diamond (UNCD) surfaces were measured using atomic force microscopy. Cell adhesion forces increased by several times on the hydrogenated diamond surfaces after UV irradiation of the surfaces in air or after functionalization with undecylenic acid. A direct correlation between initial cell adhesion forces and the subsequent cell growth was observed. Cell adhesion forces were observed to be strongest on UV-treated UNCD, and cell growth experiments showed that UNCD was intrinsically more biocompatible than microcrystalline diamond surfaces. The surface carboxylic acid groups on the functionalized diamond surface provide tethering sites for laminin to support the growth of neuron cells. Finally, using capillary injection, a surface gradient of polyethylene glycol could be assembled on top of the diamond surface for the construction of a cell gradient.     

Improving neuron-to-electrode surface attachment via alkanethiol self-assembly: an alternating current impedance study

In this work, the omega-amine alkanethiols, cysteamine (CA) and 11-amino-1-undecanethiol (11-AUT), were chemisorbed as self-assembled monolayers (SAMs) onto 250-microm gold microelectrodes that were microlithographically fabricated within eight-well cell culture plates and investigated as a means to improve neuron-to-electrode surface attachment (NESA). Dynamic contact angle (DCA) measurements showed similar advancing, theta(a) (69 degrees and 65 degrees ), but contrasting receding contact angles, theta(r) (9 and 30 degrees ) for CA- and 11-AUT-SAMs, respectively. The corresponding hysteresis (Deltatheta(ar) = 60 and 35 degrees, respectively) indicates the CA-SAM displays greater amphiphilic character than the 11-AUT-SAM. A portion of the greater Deltatheta(ar) for CA-SAMs may arise from surface heterogeneity, as compared to sputter-deposited gold and 11-AUT-SAMs. Tapping mode atomic force microscopy (AFM) confirmed a 6% increase (CA-SAM) and a 22% decrease (11-AUT-SAM) in surface roughness when compared to clean but unmodified, sputter-deposited gold. The extracellular matrix cell adhesion proteins, collagen, fibronectin, and laminin, were covalently coupled to the aminoalkanethiol-decorated gold electrodes via acid-amine heterobifunctional cross-linking. Using fluorescein isothiocyanate-tagged laminin, confocal fluorescence microscopy of both CA- and 11-AUT-SAM-modified and unmodified gold microelectrodes confirmed coupling of the protein to the electrode and was readily distinguishable from nonspecifically adsorbed protein. DCA measurements of laminin physisorbed directly onto gold or covalently immobilized via CA- or 11-AUT-SAM had similar advancing (ca. 63-65 degrees ) and receding (ca. 7-9 degrees ) contact angles. Tapping mode AFM of these protein-bearing surfaces likewise showed dimerized protein aggregates of similar surface roughness. PC-12 cells cultured to confluence on both unmodified and SAM-modified, protein-derivatized gold microelectrodes were examined by alternating current impedance (50 mV p-t-p at 4 kHz). CA- and 11-AUT-SAM-modified surfaces when serving as a foundation or covalently immobilized adhesion proteins produced highly stable and reproducible temporal impedance responses. On the basis of the magnitude and the reproducibility of the impedance responses, the CA-SAM-modified surfaces were identified as being best suited for optimal neuron-to-electrode contact with laminin. Laminin performed best when compared to collagen and fibronectin. Covalent immobilization of the adhesion-promoting proteins results in enhanced NESA by tightly anchoring cells to the electrode.     

Surface plasmon resonance study on the interaction between the fructose and phenylboronic acid monolayer

Phenylboronic acid derivatives were synthesized and their self-assembled monolayers (SAMs) were formed on a gold surface. The interaction between fructose and phenylboronic acid monolayers was evaluated using surface plasmon resonance (SPR). These phenylboronic acid monolayers showed good sensitivity to fructose at a low concentration range and the resonance angle shifts increased in accordance with the alkyl chain length.     

Quantifiable correlation of ToF-SIMS and XPS data from polymer surfaces with controlled amino acid and peptide content

Peptide-coated surfaces are widely employed in biomaterial design, but quantifiable correlation between surface composition and biological response is challenging due to, for example, instrumental limitations, a lack of suitable model surfaces or limitations in quantitatively correlating data from different surface analytical techniques. Here, we first establish a reference material that allows control over amino acid content. Reversible addition-fragmentation chain-transfer (RAFT) polymerisation is used to prepare a copolymer containing alkyne and furan units with well-defined chain length and composition. Huisgen Cu(I)-catalysed azide-alkyne cycloaddition reaction is used to attach the model azido-polyethyleneglycol-amide-modified pentafluoro-l -phenylalanine to the polymer. Different compositional ratios of the polymer provide a surface with varying amino acid content that is analysed by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). Nitrogen-related signals are compared with fluorine signals from both techniques. Fluorine and nitrogen signals from both techniques are found to be related to the copolymer compositions, but the homopolymer data deviate from this trend. The approach is then translated to a heparin-binding peptide that supports cell adhesion. Human embryonic stem cells cultured on copolymer surfaces presenting different amounts of heparin-binding peptide show strong cell growth while maintaining pluripotency after 72 h of culture. The early cell adhesion at 24 h can be correlated to the logarithm of the normalised CH₄N⁺ ion intensity from ToF-SIMS data, which is established as a suitable and generalisable marker ion for amino acids and peptides. This work contributes to the ability to use ToF-SIMS in a more quantitative manner for the analysis of amino acid and peptide surfaces.     

Covalent attachment of organic monolayers to silicon carbide surfaces

This work presents the first alkyl monolayers covalently bound on HF-treated silicon carbide surfaces (SiC) through thermal reaction with 1-alkenes. Treatment of SiC with diluted aqueous HF solutions removes the native oxide layer (SiO2) and provides a reactive hydroxyl-covered surface. Very hydrophobic methyl-terminated surfaces (water contact angle theta = 107 degrees ) are obtained on flat SiC, whereas attachment of omega-functionalized 1-alkenes also yields well-defined functionalized surfaces. Infrared reflection absorption spectroscopy, ellipsometry, and X-ray photoelectron spectroscopy measurements are used to characterize the monolayers and show their covalent attachment. The resulting surfaces are shown to be extremely stable under harsh acidic conditions (e.g., no change in theta after 4 h in 2 M HCl at 90 degrees C), while their stability in alkaline conditions (pH = 11, 60 degrees C) also supersedes that of analogous monolayers such as those on Au, Si, and SiO2. These results are very promising for applications involving functionalized silicon carbide.     

Effect of interfacial molecular recognition of non-surface-active species on the main characteristics of monolayers

Recent progress in studies of the main characteristics of supramolecular assemblies formed by interfacial molecular recognition between an amphiphilic monolayer and a non-surface-active species, which is dissolved in the aqueous subphase, by complementary hydrogen bonding and/or electrostatic interaction at the air-water interface is reviewed. Systems consisting of an amphiphilic melamine-type monolayer and an pyrimidine derivative dissolved in the aqueous subphase are representative model systems for molecular recognition on the basis of complementary hydrogen bonding. Most of the studies have been performed with 2,4-di(n-undecylamino)-6-amino-1,3,5-triazine (2C11H23-melamine) monolayers as host component and thymine, uracil or barbituric acid as dissolved non-surface-active pyrimidine derivatives. The combination of surface pressure studies with Brewster angle microscopy (BAM) imaging and Grazing incidence X-ray diffraction (GIXD) measurements is optimal for the characterization of the change in structure and phase behavior at the interfacial recognition process. The molecular recognition of all pyrimidine derivatives dissolved in the aqueous subphase changes drastically and in a specific way the characteristic features (pi-A isotherms, morphology of the condensed phase domains) of the 2C11H23-melamine monolayer. The small condensed phase domains of the pure 2C11H23-melamine monolayer are compact without an inner texture. The monolayers of the supramolecular 2C11H23-melamine entities with thymine or uracil form specifically well-shaped condensed phase domains with an inner alkyl chain texture essentially oriented parallel to the periphery. The completely different morphology of the 2C11H23-melamine-barbituric acid monolayers is characterized by the formation of large homogeneous areas of condensed phase that transfer at smaller areas per molecule to a homogeneous condensed monolayer. The striking differences in the main characteristics between the supramolecular entities are related to their different chemical structures: complementary hydrogen bonding of two thymine or uracil molecules by one 2C11H23-melamine molecule and a linearly extended hydrogen bonding network between 2C11H23-melamine and barbituric acid. The high values of hydrogen bonding energy obtained by quantum chemical calculations on the basis of the semi-empirical PM3 method state the high stability of the supramolecular entities. The GIXD results reveal that the formation of hydrogen-bond based superstructures between the polar head groups of the amphiphilic 2C11H23-melamine monolayer and the non-surface-active pyrimidine derivatives gives rise only to quantitative changes in the two-dimensional lattice structure of the alkyl chains. The alternative possibility to construct interfacial molecular recognition systems on the basis of acid-base interaction is demonstrated by the experimental results obtained by molecular recognition of the heptadecyl-benzamidinium chloride monolayers with dissolved non-surface-active phenylacetate ions. The formation of supramolecular assemblies causes also drastical changes of the surface features in these systems. Here, the development of a substructure in the condensed phase domains consisting of long filigree strings and the favoured formation of bilayers overgrowing the strings indicates a linearly extended amidinium-carboxylate interfacial structure of the base and acid component in alternating sequence.     

分子动力学模拟多巴在自组装膜上的黏附性

为了更好地理解贻贝在表面的黏附机理,实现水下胶黏,采用分子动力学方法研究了多巴在自组装膜上的黏附性:采用伞形取样和加权柱状图分析方法计算了多巴在不同自组装膜表面的黏附自由能,使用拉伸分子动力学模拟研究了多巴在不同自组装膜表面上黏附后的脱附力.结果表明,多巴在带负电的羧基自组装膜上的黏附能比在带正电的氨基自组装膜上的大,多巴更容易黏附到带负电表面;多巴在带电表面的黏附能比未带电表面的黏附能更强,表明在带电表面黏附更稳定.进一步分析了多巴在不同表面的取向分布,发现多巴与不同表面相互作用的方式不同:与疏水表面主要通过苯环相互作用;与亲水表面主要通过羟基相互作用;与负电表面主要通过氨基相互作用;与正电表面主要通过羧基相互作用.通过模拟比较了多巴在不同自组装膜上的脱附力,发现多巴在带电表面的脱附力比在未带电表面的大,与黏附能的趋势一致.对比4种非带电表面的脱附力,发现多巴在疏水性甲基自组装膜表面的脱附力最大,黏附更稳定,随着表面疏水性的增加,脱附力增大,黏附稳定性增强.本工作可为研发新型水下胶黏剂提供理论指导.     

Protein interactions with model chromatographic stationary phases constructed using self-assembled monolayers

Model surfaces representative of chromatographic stationary phases were developed by immobilising an homologous series (C2-C18) of n-alkylthiols, mixed monolayers of C4/C18 and thioalkanes with alcohol, carboxylic acid, amino and sulphonic acid terminal groups onto a flat, silver-coated glass surface using self-assembled monolayer (SAM) chemistry. The processes of adsorption and desorption of serum albumins onto the monolayer surfaces was monitored in real-time using surface plasmon resonance (SPR). Alkyl-terminated SAMs all showed a strong adsorption of bovine serum albumin which was largely independent of alkyl chain length, the ratio of mixed C4/C18 SAMs or the solution pH/ionic strength. The adsorption of human serum albumin to carboxylic and amine terminated SAMs was shown to be predominantly via non-electrostatic interactions (hydrophobic or hydrogen bonding). However, sulphonic acid terminated SAMs showed almost exclusively electrostatic interactions with human serum albumin. This preliminary work using self-assembled monolayer chemistry confirms the usefulness of well characterised SAMs surfaces for investigating protein adsorption and desorption onto/from model chromatography surfaces and gives some guidance for selecting appropriate functionalities to develop better surfaces for chromatography and electrophoresis.     

Studies of monolayer/substrate adhesion as function of the monolayer headgroup charge: DMPE and DMPA

The variation of the work of adhesion between lipid monolayers and a plane silicon oxide surface in a typical LB-configuration is measured as function of the subphase pH. The adhesion energy is deduced via fluorescence microscopy from the equilibrium meniscus height. With increasing pH the negative headgroup charge of both, dimyristoylphosphatidylethanolamine (DMPE) and dimyristoylphosphatidic acid (DMPA) monolayers increases. The increasing charge of DMPE is reflected in a measured decrease of the work of adhesion at higher pH. The DMPA/SiO₂ interaction is not affected by increasing headgroup charges. These results are qualitatively understood in terms of an electrostatic double layer interaction between charged surfaces. It predicts decreasing adhesion for increasing, but low surface charge densities (DMPE). whereas the adhesion is constant for high surface charge densities (DMPA).     

Interfacial Behaviors of Azocalixarene Derivatives at the Air/Water Interface and Photochromism in the Langmuir-Blodgett Films

The azocalixarenes is a novel chromogenic compound and their spectra properties have been reported. A number of them have been applied as selective ionophores in extractive process1 or as selective ligands in ion selective electrodes and optical sensors based on spectra changes2. Some amphiphilic azocalixarene derivatives with hydrophobic long alkyl chains were synthesized and their interfacial behaviors at the air / water interface have also been investigated3. However, the photochromism of t…     

First reaction of a bare silicon surface with acid chlorides and a one-step preparation of acid chloride terminated monolayers on scribed silicon

Methyl-terminated and acyl chloride terminated monolayers are produced when silicon is scribed under mono- and diacid chlorides, respectively. To the best of our knowledge, this is the first report of the reaction between a bare silicon surface and acid chlorides. This reaction takes place by wetting the silicon surface in the air with the acid chloride and scribing. Scribing activates the silicon surface by removing its passivation layer. We propose that scribed silicon abstracts chlorine from an acid chloride to form an Si-Cl bond and that the resulting acyl radical diffuses back to the surface to condense with the surface and form an alkyl monolayer. X-ray photoelectron spectroscopy (XPS) confirms the presence of chlorine and shows a steady increase in the amount of carbon with increasing alkyl chain lengths of the acid chlorides. Time-of-flight secondary ion mass spectrometry shows SiCl(+) species and a steady increase in representative hydrocarbon fragments with increasing alkyl chain lengths of the acid chlorides. XPS indicates that diacid chlorides react primarily at one of their ends to create acyl chloride terminated surfaces in a single step. The resulting surfaces are shown to react with various amines (piperazine, morpholine, and octylamine) and a protein. Calculations at Hartree-Fock and density functional theory levels are consistent with the proposed mechanism.     

The interactions between doxorubicin and amphiphilic and acidic β-sheet peptides towards drug delivery hydrogels

Amphiphilic β-sheet peptides decorated by acidic amino acids may spontaneously assemble into ordered monolayers at interfaces as well as form hydrogels at near physiological pH values. Here we monitored interactions between the peptide Pro-Asp-(Phe-Asp)(5)-Pro and the mildly amphiphilic chemotherapeutic drug doxorubicin (Dox). The peptide in the form of monolayers at the air water interface was found to enhance Dox adsorption, pointing to favorable interactions between the amphiphilic peptide and Dox. In solutions the fluorescence emission of Dox which was fitted to the Stern-Volmer quenching models suggested the formation of Dox associated forms >25 μM and larger forms at >100 μM. In presence of the peptide these larger associated forms appeared already at Dox concentrations >50 μM, indicating enhanced interactions between Dox and the peptide in the β-sheet conformation. Peptide hydrogels loaded with the drug showed sustained release profiles over several days. Smaller fractions of the drug were released with increase in either peptide or initially loaded drug concentrations. The released Dox was found to retain its cytotoxic activity in vitro. This study provides insights on the interactions between the amphiphilic and acidic peptide and Dox that are useful for the bottom up development of Dox-loaded peptide hydrogels for local drug delivery applications.     

Synthesis of Amphiphilic Fullerene Derivatives and Their Incorporation in Langmuir and Langmuir‐Blodgett Films

Various amphiphilic fullerene derivatives were prepared by functionalization of [5,6]fullerene‐C₆₀‐I_h (C₆₀) with malonate or bis‐malonate derivatives obtained by esterification of the malonic acid mono‐esters 5 – 7 . Cyclopropafullerene 10 was obtained by protection of the carboxylic acid function of 6 as a tert‐butyl ester, followed by Bingel addition to C₆₀ and a deprotection step (Scheme 2). The preparation of 10 was also attempted directly from the malonic acid mono‐ester 6 under Bingel conditions. Surprisingly, the corresponding 3′‐iodo‐3′H‐cyclopropa[1,9][5,6]fullerene‐C₆₀‐I_h‐3′‐carboxylate 11 was formed instead of 10 (Scheme 3). The general character of this new reaction was confirmed by the preparation of 15 and 16 from the malonic acid mono‐esters 13 and 14 , respectively (Scheme 4). All the other amphiphilic fullerene derivatives were prepared by taking advantage of the versatile regioselective reaction developed by Diederich and co‐workers which led to macrocyclic bis‐adducts of C₆₀ by a cyclization reaction at the C‐sphere with bis‐malonate derivatives in a double Bingel cyclopropanation. The bis‐adducts 37 – 39 with a carboxylic acid polar head group and four pendant long alkyl chains of different length were prepared from diol 22 and acids 5 – 7 , respectively (Scheme 9). In addition, the amphiphilic fullerene derivatives 45, 46, 49, 54 , and 55 bearing different polar head groups and compound 19 with no polar head group were synthesized (Schemes 11–13, 15, and 5, resp.). The ability of all these compounds to form Langmuir monolayers at the air‐water interface was investigated in a systematic study. The films at the water surface were characterized by their surface pressure vs. molecular area isotherms, compression and expansion cycles, and Brewster‐angle microscopy. The spreading behavior of compound 10 was not good, the two long alkyl chains in 10 being insufficient to prevent aggregation resulting from the strong fullerene‐fullerene interactions. While no films could be obtained from compound 19 with no polar head group, all the corresponding amphiphilic fullerene bis‐adducts showed good spreading characteristics and reversible behavior upon successive compression/expansion cycles. The encapsulation of the fullerene in a cyclic addend surrounded by four long alkyl chains is, therefore, an efficient strategy to prevent the irreversible aggregation resulting from strong fullerene‐fullerene interactions usually observed for amphiphilic C₆₀ derivatives at the air‐water interface. The balance of hydrophobicity to hydrophilicity was modulated by changing the length of the surrounding alkyl chains or the nature of the polar head group. The best results in terms of film formation and stability were obtained with the compounds having the largest polar head group, i.e. 45 and 46 , and dodecyl chains. Finally, the Langmuir films obtained from the amphiphilic fullerene bis‐adducts were transferred onto solid substrates, yielding high‐quality Langmuir‐Blodgett films.     

Two-dimensional arrays of amphiphilic Zn2+-cyclens for guided molecular recognition at interfaces

The sterically guided molecular recognition of nucleobases, phosphates, adenosine, and uridine nucleotides on Langmuir monolayers and Langmuir-Blodgett monolayers of amphiphilic mono- or bis(Zn2+-cyclen)s assembled on thiolated surfaces was investigated. The stepwise selective binding of metal ions, uracil, or phosphate by dicetyl cyclen monolayers with variously tuned structures at the air/water interface was corroborated by the measurements of the corresponding LB films deposited onto quartz crystals. Two types of recognition surfaces were fabricated from Zn2+-dicetyl cyclen. The surface covered with a complex preformed in the Langmuir monolayer was capable both of imide and of phosphate binding. The similar complex formed directly in an LB film on thiolated gold was inactive with respect to imide. The surface plasmon resonance measurements evidenced the stepwise assembly of complementary nucleotides on SAM/LB templates through consecutive phosphate-Zn2+-cyclen coordination. Base pairing between nucleotides resulted in a formation of A-U bilayers comprising two complementary monolayers. Finally, we report on SAM/LB patterns designed for divalent molecular recognition of uridine phosphate by amphiphilic bis(Zn2+-cyclen).     

Four-Component Ugi Reaction for Optical Chirality Sensing and Surface Nanoengineering of Chiral Self-Assemblies

Using green chemistry to control chirality at hierarchical levels as well as chiroptical activities endows with new opportunities to the development of multiple functions. Here, the four-component Ugi reaction is introduced for the general and precise optical chirality sensing of amines as well as the surface nanoengineering of chiral soft self-assemblies. To overcome the relatively weak Cotton effects, direct synthesis of a folded peptide structure on a rotatable ferrocene core with axial chirality was accomplished from chiral amine, 1,1’-ferrocenyl dicarboxylic acid, formaldehyde and isocyanide. Enhanced Cotton effects benefiting from the folded structure allow for the precise and quantitative sensing of natural and synthetic chiral amines covering alkyl, aromatic amines and amino acid derivatives. In addition, aqueous reaction enables the modification of amine-bearing dye to microfibers self-assembled from π-conjugated amino acids. Surface dye-modification via Ugi reaction barely changes the pristine morphology, showing non-invasive properties in contrast to dye staining, which is applicable in soft nano/microarchitectures from self-assembly. This work which combines the four-component Ugi reaction to enable precise ee% detection and surface nanoengineering of soft chiral assemblies sheds light on the advanced application of green chemistry to chirality science.     

Interaction of a laminin derived peptide with phosphatidyl choline/phosphatidyl glycerol

The physicochemical interactions between an active peptide sequence derived from laminin and phospholipids have been studied. The main aim is to determine the suitability of this peptide fragment to be linked to liposome's with the purpose to develop targeting devices. Results indicate that this peptide is able to insert in lipid monolayers and also to form monomolecular layers at an air/water interface. Besides, miscibility studies carried out through compression isotherms of mixed monolayers [dipalmitoyl phosphatidylcholine (DPPC)/peptide], indicate a strong interaction at 60-80% DPPC molar composition. Studies carried out with lipid bilayers indicate that the interaction is restricted to the external face of the vesicles. Moreover, the presence of this peptide in the incubation media promotes a low level of carboxyfluorescein (CF) leakage and no fusion of vesicles. These results indicate that the association of this sequence to vesicles do not produce damage of the bilayer and can be used as potential targeting vector.