KR20140082970A - Peptide nanostructure and a production method therefor - Google Patents

Abstract

The present invention provides a compound of a chemical formula 1. A thin film or a nanostructure can be simply formed to have excellent material properties and a high applicability by enabling the compound of the chemical formula 1 to stably form a self-assembly peptide nanostructure through an alignment of peptides. The peptide nanostructure according to the present invention can be usefully used to manufacture an organic electronic material or a bio material.

Description

The present invention relates to a peptide nanostructure and a production method thereof,

The present invention relates to a peptide nanostructure and a method for producing the same.

There is a great need to develop new organic electronic materials required for the industry, including organic light emitting diodes. In addition, existing mineral-based materials are difficult to lightweight and large-scale thin, and the cost of raw materials is increasing due to the depletion of rare resources. Especially recently, as touch panels have become the mainstay of the display industry, it is urgent to secure alternative materials for materials used as transparent electrodes.

Indium tin oxide (ITO), which is currently used as a transparent electrode, is expected to be depleted in the next few years (cited in Kato et al., Nat. Commun. 3, 645 (2012), Physics and Advanced Technology June 2012) It is very urgent to replace indium tin oxide with an organic material in the state that it enters the electrode. Currently, organic materials are partially used industrially, but only a small part of them are expected to be replaced with organic materials or polymer materials in the future.

Materials used to store or convert solar energy as an alternative energy source are also ultimately replaced by organic materials due to resource depletion. However, currently developed organic electronic materials have low yield and efficiency, And the production cost is high. Specifically, it is difficult to modify carbon nanotubes (CNTs). Single-wall carbon nanotubes (CNTs) are difficult to commercialize due to difficulty in mass production. In the case of Graphene Although it is emerging as a new material to replace ITO, in order to commercialize transparent electrodes, excellent quality, large-area production, and adhesion to a substrate are required.

Therefore, although efforts are made to make two-dimensional nanostructures using polymers or organic materials, there is no clear result in the commercialization stage. One of them is a nano structure formation technique using a peptide which is a biomaterial.

U.S. Patent No. 7,179,784 relates to surfactant peptide nanostructures and uses thereof, and discloses the use of nanotubes and drug delivery using the oligopeptides having dipolar sequences.

U.S. Patent No. 7,491,699 relates to peptide nanostructures and methods of making the same, and discloses a spherical structure formed using a peptide consisting of four amino acids including aromatic side chains and uses thereof.

However, the level of research on peptide nanostructures is at an early stage and there is a need for the development of various nanostructures using peptides and their application areas, as compared to the degree of understanding of the formation mechanism.

The present invention has been made to solve the above problems, and it is an object of the present invention to provide a peptide capable of forming a nanostructure by self-assembly, a nanostructure using the same, and a method for producing the same.

In one aspect, the invention provides compounds of formula 1,

X ¹ a-Y n -X ² b wherein X ¹ and X ² are each independently a D- or L-type natural or unnatural amino acid or derivative thereof having a side chain capable of pi-phi interactions, ¹ and X ² are the same or different and Y is a D- or L-type natural or unnatural amino acid or derivative thereof having charged side chains or nucleophilic side chains capable of forming a bridge, a and b are each the same And n is an integer of 1 to 10,

In another aspect, the present invention relates to self assembled nanostructures comprising at least one of the compounds of formula (I). The self-assembled nanostructure may further include a monomer for the production of the conductive polymer film.

In another embodiment, the present invention relates to a method for preparing a self-assembled nanostructure using the compound of formula (1). The method comprises reacting the compound of Formula 1 under conditions favoring the formation of the self-assembled nanostructure.

In another embodiment, the present invention is directed to a conductive polymer film comprising a compound of Formula 1 and a monomer.

In another aspect, the present invention relates to a method for preparing a conductive polymer film using the compound of Chemical Formula 1, which comprises reacting a compound of Chemical Formula 1 with a monomer. The method comprises reacting the compound of formula (I) and the monomer under conditions favoring the formation of self-assembled nanostructures.

The peptide nanostructure comprising the compound of formula (1) according to the present invention is useful as a platform for manufacturing nanostructures having various functions in water or various organic inorganic buffer solutions, A polymer conductive film, and the like. In addition, the nanostructure according to the present invention may have various conductivities according to the type of the adopted sequence, and can control the thickness of the nanostructure according to the control of the reaction time, And can be used not only as an organic electronic material but also as a tunable peptide lens for various purposes, a floating hydrophobic scaffold for cell culture, a reactive drug delivery vehicle, an ion selective membrane, a regular conductive polymer, And a biocomponent such as a catalyst based on tyrosine.

1 shows a peptide nanostructure formed of a peptide of the YYACAYY sequence according to one embodiment of the present invention. (A) is an optical microscope photograph (magnification: 50 times) taken in terms of shape change over time of the dropped peptide solution, and the bright region in the center is due to backlight transmission. A total of 80 μl of YYACAYY solution (2 mM) was dropped onto the slide glass, and a flat facet was formed on the upper surface over time. (B) shows an oblique observation of the dripped peptide solution by an optical microscope, showing a clear boundary formed on the upper surface by the flat surface peptide nanostructure. (C) is a transmission electron microscope (TEM) image of a film formed with a 2 mM concentration of peptide. (D) is a photograph of a peptide film formed in a 10-cm-diameter petri dish with a large and thick film over the entire water / air interface when 10 ml of 2 mM peptide was added. (E) is a diagrammatic representation of the process of forming a planar surface, in which dense horizontal association mediated by the tyrosine of peptides floating at the air / water interface, vertical growth of disulfide bonds and a plurality of thin nanosheets And the formation of a flat plane through the surface.
Figure 2 shows a peptide nanostructure formed of a peptide of the YYCYY sequence according to another embodiment of the present application. (A) shows a flat surface structure formed on the upper surface by dropping 80 쨉 l of peptide solution (2 mM) on a slide glass, left for 30 minutes in air, and observed from the side by an optical microscope. (B) was a TEM image of the peptide nanostructure formed in (A), and the formed film was transferred to a carbon-coated grid and then subjected to a negative amber color with aqueous solution with 2% uranyl acetate. (C) is the same as in (A) but reacted in a non-oxidizing environment (desiccator). Unlike (A), no nanostructure was formed, indicating that the oxygen environment is important for the formation of a flat surface.
FIG. 3 is a photograph of a film nanostructure formed of a peptide having a sequence of YYCYY (A, B) or YYACAYY (C) stained with a fluorescent coloring reagent. The coloring reagent is Nile Red, which binds to a hydrophobic chemical substance, (B) and (C) of thioflavin-T (Th-T) reagent that penetrates into the nanoparticles of the protein or peptide.
Figure 4 shows the effect of pH on the formation of a flat surface. (A) is a graph showing the time taken for 80 [mu] l of YYACAYY peptide (1 mM) to form a flat surface of 2 mm at different pH values. Under pH 3.3, peptides did not dissolve and white agglutinates were formed. When the pH was above 8, no flat surface was formed, and the most effective flat surface was formed at about pH 5 corresponding to the equipotential point of the peptide used, that is, pH 5.8 .
Figure 5 shows the effect of the volume of solution used for peptide nanostructure formation on the rate of planar surface formation. Different volumes of the solution were dropped onto the glass and the time until the size of the flat surface reached 2 mm was measured. The lower the drop volume, the higher the flatness rate, which is believed to be due to the accelerated evaporation of water at the interface where the film is formed, which suggests that the rate of evaporation of water during film formation affects the rate of film formation This means that the larger the size of the water droplet, the longer it takes to evaporate, so that the rate of film formation is estimated to decrease. On the other hand, when the volume decreases below 20 μl, the flat surface formation rate slows down as the surface tension increases relatively.
FIG. 6 is a graph showing the peptide concentration and the tendency (number of times) of film and nanofiber formation according to the assembly region in which the nanostructure is formed, using TEM and AFM measurement results. The minimum concentration of film formation was 0.22 mM, and film formation was also increased with increasing concentration. The nanofibers were formed on the bulk at a minimum concentration of 0.33 mM. The flat plane structure was observed at a concentration of 0.44 mM or more.
Figure 7 shows the effect of the number of tyrosine in the peptide on the formation of a flat plane. The relative formation rates of the planar surface were monitored at different concentrations (0.33, 0.55, 1.10, 1.65, and 2.20 mM of peptide (50 mM HEPES, pH 7.4) for each peptide with YCY, YYCYY and YYYCYYY sequences. The relative velocities were determined based on YYCYY (1.1 mM) and compared. YCY did not form a film due to the lack of pi-pi interactions. (B) shows that YYCYY effectively forms a flat plane (single flat plane) at concentrations above 1.1 mM (C) shows that YYYCYYY forms a corrugated flat plane at 1.1 mM. This is due to the pi-pi interactions due to the additional tyrosine present. This indicates that if the functional group of tyrosine is changed, the shape of the final material can be changed by controlling the pi-pi interactions.
Figure 8 shows the chemical and structural analysis results of the formed peptide films. (A) is an AFM image showing a structure in which nanosheets are stacked in layers (film formation for 20 minutes, Z range: 10 nm). (B) shows the vertical growth of the peptide film as a function of time. (C) is a result of XRD analysis after collecting the formed films as powder, and the graph in the graph is an enlarged view of the range of 13 to 56 degrees in the 2θ range. (D) represents a Raman spectrum of a monomeric peptide (black line) and a film (blue line). (*) Represent tyrosine peaks, and 503 cm ^-1 and 2568 cm ^-1 peaks represent -SS-bond and sulfhydryl group (-SH). The Raman signal in the range of 460-540 cm ^{- 1} was magnified in the graph.
9 is an AFM image of a YYACAYY film having a multilayer structure. (A) is a photograph of a film transferred from the interface to mica after 20 minutes from the start of film formation, and the edge shows a stepped shape. This indicates that the nanosheets of the single layer are continuously stacked to form a multilayered structure with a sharp edge and a flat surface indicating that the nanosheet has a well-ordered structure. (B) shows that the formed peptide film is uniform, smooth and has a thickness of 320 nm to 365 nm. The film thickness increased with time. 80 [mu] l of peptide solution (2 mM) in silicone-treated glass was left for 30 minutes to form a flat surface, and the formed film was transferred to mica and analyzed.
10 is an AFM image of a thin film formed by a peptide of YYACAYY. The membrane has a thickness of about 1.4 nm (1.1 mM, Z range: 10 nm) and the graph in the image is the cross-sectional analysis of the red line.
Figure 11 is a TEM image of a film formed using YYACAYY peptide at different concentrations (0.11-1.1 mM). (A) is a schematic representation of the location of the sample taken at the air / water interface for TEM analysis. (B) shows images of nanostructures formed at different concentrations, taken 30 minutes after the start of film formation, showing an increase in film size with increasing concentration. The minimum amount required for film formation is about 0.22 mM. It can be seen that the thickness increases as well as the lateral expansion as the concentration increases. At 1.1 mM, the size of the film grows to cover the entire area of the grid (97 μm × 97 μm).
12 is a TEM image of coexisting nanofibers formed using a YYACAYY peptide. (A) is a schematic representation of the location of the sample taken from the bulk phase solution for TEM analysis. (B) are TEM images of the peptides at different concentrations of 0.33, 1.1, and 1.43 mM. This suggests that formation of nanofibers is preferred in the bulk phase, and film formation is preferred in the water-air interface, thereby determining the type of nanostructure formed depending on the position of the peptide. This is because at the interface, the hydrophobic tyrosine residues of the peptide are arranged on one plane due to the presence of the air phase, and the tyrosine positions are different in the bulk phase to form nanofibers. The formation of nanofibers started at a concentration of 0.33 mM and the amount of nanofibers formed as the concentration increased. When the concentration exceeded about 1.43 mM, twisted nanofibers were formed and wound together in a helix form.
Fig. 13 shows the results of X-ray diffraction analysis of YYACAYY peptide. Since the film is not a single crystal and is difficult to analyze at the atomic level, it is matched with the known protein structure and the calculation results by the present inventors. The large and strong peak at 13.5 Å represents the thickness of the layer, which is close to the typical thickness of 14.0 Å observed in the thinnest layer by AFM analysis. 6.8 A represents the Cα-Cα 'distance, which is the interval between the cysteine residues of the YYACAYY dimer linked by a disulfide bond (Cα-CH ₂ -SS-CH ₂ -Cα'), similar to the typical interval found in conventional proteins Do. The 4.8 Å spacing is similar to the distance of the face-to-edge structure in the tyrosine-tyrosine bond. The 3.4 Å spacing corresponds to the diameter of the a-helix strand in the backbone direction.
Fig. 14 shows the mechanism of nanostructure formation of a peptide having a YYACAYY sequence. (A) represents the chemical structure of YYACAYY. (B) is a result of a simulation (500-ps molecular dynamics) of the conformation of the peptide with the YYACAYY sequence. The hydrophobic phenol ring (red) and the sulfhydryl group (-SH) Is located. (C) shows the structure of the YYACAYY peptide dimer observed in two different aspects. Indicates that the plane formed by two Tyr2 and two Tyr6 is perpendicular to the plane formed by two Tyr1 and two Tyr7. (D) shows the structure of the YYACAYY peptide assembled transversely, and the four neighboring dimers are associated by tyrosine mediated pi-pi interactions, indicating that nanosheets are continuously deposited. The dotted line is an enlargement of the interaction between the hydroxyl group of the phenol group of Tyr1 and the plane of the phenol group of Tyr7. Tyr2 and Tyr6 were expressed using a ball-and-stick model. (E) is the detailed structure of the YYACAYY peptide grafted horizontally. It is the result of analyzing the geometrical structure of two dimers (YYACAYY - YYACAYY) in order to understand the mechanism of association between peptides in the film formation process. The helix structure is green, the tyrosine residue is red, and the dimer is blue. Each monomer was designated A, B, C, and D, respectively. When the first dimer (left A, B) is closely packed with the second dimer (right C.D), Tyr7 of monomer A is associated with Tyr1 of monomer C through face-to- , And this action is equally applied to Tyr1 of monomer B and Tyr7 of monomer D. Tyr2 and Tyr6 are represented by the ball-and-stick model. (F) is a nanosheet structure in which dimeric peptides associated with pi-pi interactions are successively stacked.
15 shows the results of HPLC-ESI mass spectrometry of YYACAYY monomers and films. (A) shows that the monomer (purity:> 97%) before forming the nanostructure has a peak at 8.78 min and mass data (916.5). (B) showed a new peak at 10.88 min as a result of the formation of the nanostructure by the peptide at the water / air interface, and it was confirmed by mass spectrometry (1830.5) that there was a disulfide bond in the peptide film .
16 shows the results of MALDI-TOF (matrix-assisted laser desorption / ionization time of flight) analysis for YYACAYY monomers and formed films. The appearance of a peak corresponding to the dimer at the water / air interface after film formation indicates that crosslinking was formed by the side chain of cysteine, and this peak disappeared when dithiothreitol (DTT) was added to the peptide solution. Indicating that disulfide bonds are important for the formation of peptide nanostructured films.
17 is a graph showing the time taken to form a flat surface according to the concentration of the reducing agent. After adding various amounts of β-mercaptoethanol to the YYACAYY peptide solution at a concentration of 1.1 mM, the time required to form a flat surface of 2 mm in diameter was compared. As shown in the results, the concentration-dependent increase in the time taken to form a flat plane (the result is the result of three independent experiments, bars represent the standard deviation).
18 is a graph showing the ability of the peptide nanostructure to recover self-damage. (A) shows that the process of forming a peptide nanostructure is photographed with a black-and-white photograph of a close-up camera, indicating that the damage (17 minutes) caused by the surface tension during the formation process is restored (26 minutes). (B) shows that even if part of the peptide nanostructure formed at the interface between water and air is artificially damaged, it is restored to within 10 minutes.
FIG. 19 shows that a film nanostructure formed of a peptide of the YYCYY sequence is transferred to another substrate, which is capable of forming a large-area peptide nanostructure and can be easily transferred onto another substrate.
Figure 20 shows 2D crystals formed by YYACAYY peptide and polypyrrole. (A) is the TEM image of the multilayer sheet on the carbon grid, and (B) is the AFM analysis result. The 2D sheet was prepared by adding ammonium persulfate to the pyrrole and YYACAYY peptide (1.1 mM) solution. The morphology of the resulting film was analyzed in the Height mode of the AFM. Cross-sectional area (red line) The analysis shows that the sheet is very flat and exhibits a homogeneity of 5 nm in thickness (internal graph). (C) is the HRTEM image of the edges of the stacked and folded sheets. The acceleration voltage of the TEM was 300 kV. (D) is a high-power lattice image of a single sheet, indicating that the crystal structure is highly ordered. Represents a hexagonal pattern resulting from the Fourier transform of the image (interior).

The present inventors have found that the role of aromatic amino acids such as tyrosine is important in the formation of self-assembling peptide nanostructures, and peptides of a specific sequence including them can rapidly form various nanostructures in various environments through self-assembly .

In one embodiment, the present invention relates to compounds of formula 1 of X ¹ a-Yn-X ² b, self-assembled nanostructures comprising the same, and methods of making the same.

Wherein X ¹ and X ² are each independently a D- or L-type natural or unnatural amino acid having a side chain capable of pi-phi interactions, X ¹ and X ² are the same or different and Y is A and b are the same or different integers of 1 to 10, n is an integer of 1 to 10, and n is an integer of 1 to 10, Lt; / RTI > In one embodiment according to the present application, n is 1, and a and b are each an integer of 2 to 5, and may be the same or different. In another embodiment according to the present application, a and b are the same integer between 2 and 5.

As used herein, the term "amino acid" includes 20 natural and non-natural amino acids, amino acids that are modified in vivo after translation, such as phosphocerine and phosphothreonine; And other rare amino acids such as 2-amino adipic acid, hydroxy lysine, nor-valine, nor-leucine; Including those enriched for enhanced cell permeability or in vivo stability, including both enantiomeric D- and L-forms.

As used herein, the term natural and non-natural refers to compounds in the form found in cells, tissues or in vivo, the latter of which means that artificial modifications have been made to these compounds for various purposes.

As used herein, the term "peptide" is intended to include both native amino acids or their degradation products, synthetic peptides, recombinantly produced peptides, peptide mimetics (typically synthetic peptides), and peptoids and semipeptides Peptide analogs and modifications to enhance cell permeability or in vivo stability. Such modifications include, but are not limited to, N-terminal modifications, C-terminal modifications, peptide bond modifications such as CH ₂ -NH, CH ₂ -S, CH ₂ -S═O, CH ₂ -CH ₂ , Side chain modifications. Methods for preparing peptide mimetic compounds are well known in the art and can be found in, for example, Quantitative Drug Design, CA Ramsden Gd., Choplin Pergamon Press (1992).

As used herein, the term "pi-pi interactions" refers to chemical bonds formed by pi electrons resulting from the superposition of two pi orbital functions. Thus, the compounds of formula (1) herein include amino acids having such interactable moieties, for example amino acids with aromatic side chains, such as tyrosine, tryptophan or phenylalanine, and variants, derivatives or analogs thereof.

As used herein, the term "cross-linking " includes covalent bonds or coordination bonds with metals, which can lead to association of molecules by bonding of adjacent peptide molecules. For example, a disulfide bond through an -SH group of an amino acid side chain, and the amino acid capable of coordination bonding with the metal is selected from the group consisting of cysteine, homocysteine, penicillamine, histidine, lysine, ornithine, arginine, aspartic acid, glutamic acid, asparagine , Or glutamine, but are not limited thereto.

In the compound of formula (I) of the present invention, X ¹ a and X ² b have an amino acid sequence of the same sequence or symmetrically symmetric with respect to Y, wherein a and b may be the same. NX ¹ X ² a-Yn-bC, as including both a CX ¹ X ² bN-Yn-direction, the amino-terminal, C- of the N- is a peptide it refers to the carboxy terminus.

The compound of formula (1) according to the present invention can form a nanostructure through stable binding through self-assembly among the compounds. In particular, in the tyrosine symmetric structure having a -SH group in the center, the pi bonds have a two-dimensional structure and can provide a bonding angle at which the layer can accumulate (see Figs. 13 to 17, etc.)

In this aspect, in another aspect, the present invention relates to a self-assembled nanostructure comprising a compound of formula (1).

The compounds of formula (1) constituting the nanostructure according to the present invention may be the same or different. A peptide having one sequence or a peptide having two or more sequences can be used in the preparation of the peptide nanostructure according to the present invention.

In one embodiment, the peptide of formula 1 herein is selected from the group consisting of YYCYY, YYYCYYY, YYACAYY, YYAACAAYY, YYGCGYY, YFCFY, FYCYF, FFCFF, YYAKAYY, YYAEAYY, YYYY, YYCYYY, YYYYY, YYDCDYY, YYAHAYY, YYHYY, YYAPAYY , Or YYPYY or a derivative thereof, but other peptide sequences forming a nanostructure having the characteristics of the present invention may also be included. In an embodiment of the present invention, the derivative includes an acyl derivative containing an acetyl group at the N-terminus or a derivative having an amide group at the C-terminus.

As used herein, the term self-assembly refers to the process by which materials such as atoms, molecules or peptides form a regular-shaped structure in a particular environment. As used herein, the term "nanostructure" is intended to include fibers, tubular, spherical, or film, having a diameter or cross section of 1 μm or less, particularly 500 nm, more particularly less than 50 nm and even more particularly less than 5 nm. And in one embodiment according to the present application is between 200 nm and 1 nm. In the case of a tubular or fiber, it means that its length is at least 1 μm, in particular at least 10 nm, more particularly at least 100 nm, even more particularly at least 500 nm.

The peptides of the present invention can be formed into various forms depending on the conditions of nanostructure formation. For example, a peptide having a concentration of 2 mM of the same sequence can be produced in a two-dimensional structure at the interface, in a solvent, or in a fiber or spherical form depending on whether it is an external stimulus (ultrasound) or not. For example, the film structure is formed at the liquid-gas interface, and the nanofibers are formed on a liquid or liquid-liquid bulk (see FIGS. 11 and 12).

Films formed from the peptides herein include facets and planar structures. The planar surface means a film formed by overcoming the surface tension of the peptide solution as shown in Fig. 1 or 2, and the face surface means a film formed along the surface of the solution maintained by surface tension.

The peptide nanostructure according to the present invention can be easily formed into a large area by self-assembly, and the peptide monomer can be structurally modified by a disulfide bond, a coordination bond by a metal ion, an ionic bond, a hydrogen bond and a hydrophobic bond with another peptide monomer It grows in a two-dimensional structure, a nanostructure, that is, a plane. Cross-linkable amino acids associate peptides through covalent bonds with other amino acids and form nanostructures with more firm planar surfaces. These bonds result in the formation of dimeric peptides, while peptide peptides are continuously accumulated due to binding of amino acid side chains capable of pi-phi interaction in the dimeric peptides and side chain edge bonds, resulting in a stable nanostructure through lateral and vertical expansion (See Figs. 13 to 17). Thus, in one embodiment, the film-form nanostructure herein has a single layer or multi-layer structure. In one embodiment, the thickness of the monolayer structure is about 1.4 nm, and if multiple layers are available, various thicknesses are possible, depending on the number of layers, in one embodiment about 50 to 400 nm (see Figures 8, 9,

The compound of Formula 1 contained in the self-assembled nanostructure according to the present invention may vary, and the rate of formation or the structure of the nanostructure may vary depending on the volume of the solution used, the sequence of the peptide, and the concentration 5, 6, and 7). In one embodiment according to the present disclosure, the self-assembled nanostructure is a flat surface and the compound of formula 1 is used at a concentration of at least about 0.1 mM, more particularly at a concentration of about 0.1 mM to 10 mM, especially at a concentration of about 0.2 mM to 10 mM, 0.22 mM. In another embodiment according to the present application, the self-assembled nanostructure is a nanofiber, and the compound of Formula 1 is used at a concentration of at least about 0.1 mM, more particularly at a concentration of about 0.1 mM to 10 mM, especially at a concentration of about 0.2 mM to 10 mM, 0.33 mM.

The nanostructures formed by the peptides according to the present invention are formed on the bulk of the liquid-gas interface or liquid-liquid. The liquid forming the liquid-gas interface according to the present invention is a volatile or non-volatile hydrophobic or hydrophilic solvent and the gas includes but is not limited to air, nitrogen, helium, hydrogen, carbon monoxide, or carbon dioxide. The liquid-liquid bulk phase according to the present invention is formed in a hydrophilic and hydrophobic liquid interface in one embodiment, and the liquid is a volatile or non-volatile hydrophobic or hydrophilic solvent.

Various solvents capable of forming the nanostructure according to the present invention can be used, and for example, the volatile or nonvolatile hydrophobic or hydrophilic solvent constituting the liquid-gas or liquid-liquid bulk phase according to the present invention can be, for example, water But are not limited to, alcohols, hydrocarbons including halogens, dimethylsulfoxide, dimethylformamide, dimethyl formacetamide, N-methylpyrrolidone, acetonitrile, tetrahydrofuran, dioxane, or organic acids .

The interface at which the nanostructure of the present invention is formed may be hydrophilic or hydrophobic. In the case of the peptide compound of the present invention, the lipophilic moiety has a lipophilic moiety, and the moiety having hydrophilicity toward the air is directed toward the aqueous solution and the molecules are aligned. In one embodiment according to the present invention, the compound of formula (I) forms a nanostructure at a pH of about 3 to 8, particularly about isoelectric point, including isoelectric point (see FIG. 4).

In another embodiment, the present invention also relates to a method of forming a self-assembled nanostructure using the compound of formula (I). The method comprises reacting the compound of formula (I) under conditions favorable for the formation of the self-assembled nanostructure of the present invention. In describing the method of the present invention, the overlapping parts of the above description are omitted in order to avoid the complexity of the description.

As described above, the self-assembled nanostructure according to the present invention may be formed into various structures in various conditions including interface conditions, concentration of peptides, and / or pH formed by various solvents and / or gases. To 12, etc.). In one embodiment according to the present disclosure, favorable conditions for the formation of the self-assembled nanostructure are those wherein the compound of formula 1 is dissolved in a liquid-gas or liquid-liquid bulk at a concentration of at least 0.2 mM, Means that the compound is reacted at a pH including the isoelectric point of the compound of formula (1) in an oxidizing atmosphere such as the above. The pH including the isoelectric point means a pH in the vicinity of the isoelectric point, which is about pH 4 with respect to the pI of each peptide used for forming the nanostructure, and is about pH 3 to 8 in one embodiment according to the present invention.

The monolayer of the unit peptide nanostructure according to the present invention has a thickness of about 1.4 nm. As the monomer / dimer remaining in the solution continues to undergo nanostructuring reaction over time, the layer is piled up on the formed nanostructure and thickened do. This process can be confirmed by matching the thickness of the theoretical peptide nanostructure with the thickness of the experimental peptide nanostructure. Therefore, the thickness of the present peptide nanostructure can be controlled according to the reaction time (see FIGS. 8 to 10).

It is also possible to control the type of the nanostructure to be formed, as described above. In one embodiment according to the present application, for example, the self-assembled nanostructure is a film or nanofiber structure, the film is formed at a liquid-gas interface, and the nanofiber structure is formed on a bulk of a liquid or liquid-liquid.

In the present application, a rigid nanostructure comprising a planar surface is formed by the above-described mechanism at the liquid-gas, liquid-liquid interface. In this regard, in order to form the nanostructure more quickly, an inorganic substance such as a metal ion including gold, silver, copper, zinc, iron, cobalt, and manganese is added, or an organic substance including various monomolecules or polymers is added The binding between the peptides is increased to promote the formation of the nanostructure.

While not intending to be limited to this theory, in the peptide nanostructure according to the present invention, as the molecular structure of the peptide monomer is stabilized, the amino acid having the hydrophilic group and the amino acid having the hydrophobic group are positioned opposite to each other, As you head toward the water, you will come to the surface. Thus, a peptide nanostructure having a two-dimensional structure is formed at the interface between water and air. Peptides are bound to each other via pi-pi bonding and / or hydrophobic bonding, and crosslinked to form a rigid nanostructure. As the reaction is repeated, a peptide nanostructure having a two-dimensional structure is stacked to form a multi-layered structure (see FIGS. 13 to 17).

In addition, the peptide forms a planar surface between the interface and the interface, especially between water and air, and can form a large-area nanostructure in centimeters.

Further, the present invention can also produce a conductive polymer film using a peptide self-assembled nanostructure formed by the present compound as a template (see FIG. 20). The conductive polymer film according to the present invention is mixed with various monomer materials and then produced through a polymerization process such as oxidation and has a well-aligned crystal structure.

In this respect, the present invention also relates to a method for producing a conductive polymer film using the compound of formula (1) and a monomer according to the present invention, and a conductive polymer film produced thereby.

In addition, the nanostructure formed using the compound of Formula 1 according to the present invention can be complexed with gold, silver, copper, zinc, iron, cobalt, manganese and the like, and can be simultaneously aligned in a two-dimensional structure. In the case of a peptide nanostructure added with such a metal, it may be a conductor, a semiconductor, or an insulator depending on the kind of the metal.

In one embodiment according to the present disclosure, when the peptide nanostructure according to the present invention comprises tyrosine, it can help to transfer electrons to other objects well. Accordingly, the peptide nanostructure according to the present invention can be used as an electron transfer layer / film or a nanostructure that helps to transfer electrons well. Therefore, it is necessary to use expensive metallic minerals having specific electrical properties Compared with the case. There is a great advantage in cost. This means that even if a small amount of metallic inorganic material is used in conceptually, it can be provided with superior electrical properties when applied on the nanostructure according to the present invention.

Furthermore, the flat plane between the interfaces seen in the peptide nanostructure according to the present invention is known to be involved in the intercellular fusion reaction in recent years, so that it is very important in biological applications.

In addition, the peptide nanostructure according to the present invention has an advantage that it can be produced conveniently at a relatively low production cost. Unlike, for example, indium tin oxide (ITO), carbon nanotube (CNT), and graphene production, it is possible to produce water or various organic / inorganic buffers without special equipment / equipment. It is expected that the addition of metal ions will rapidly form a solid nanostructure, which can be applied to many materials requiring metal deposition.

Hereinafter, preferred embodiments of the present invention will be described in order to facilitate understanding of the present invention. However, the following examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the following examples.

[ Example ]

[Materials and Methods]

compound

(100-200 mesh, 1.26 mmol / g) resin, 2- (1H-benzotriazol-1-yl) -1,1,3,3-tetramethyluronium hexafluoro (HIPt), hydroxybenzotriazole (HOBt) and Fmoc-protected amino acids were purchased from BeadTech (Seoul, Korea), and N, N-diisopropylethylamine (DIPEA), triisopropylsilane ), 3,6-dioxa-1,8-octanedithiol (DODT), 4- (3,6-dimethyl-1,3-benzothiazol- Dimethylaniline chloride (thiopurine), β-mercaptoethanol, HEPES buffer, eurosyl acetate, and anisole were purchased from Aldrich (USA). Dichloromethane (DCM), N, N-dimethylformamide (DMF), methanol, piperidine, diethyl ether and trifluoroacetic acid (TFA), sodium hydroxide (NaOH) (Korea) and hydrogen peroxide (H ₂ O ₂ , 30%) were purchased from Junsei (Japan).

Atomic power  microscope( Atomic force microscope , AFM ) analysis

A peptide aqueous solution drop (1 mM) was placed on a glass surface-treated glass and allowed to stand at room temperature for 30 minutes to form a peptide two-dimensional structure at the interface, and a peptide two-dimensional structure was transferred to a clean silicon wafer or mica surface to obtain a surface. To remove the salt transferred from the solvent, the peptide nanostructure adsorbed on the silicon wafer or mica surface was rinsed with distilled water and allowed to dry for 10 minutes. To obtain detailed photographs, a scanning electron microscope (Dimension 3100, Veeco Instruments, Woodbury, NY) was scanned at a rate of 0.5 Hz using a can travertip tip with a spring constant value of 21-78 N / m to obtain a peptide nanostructure Respectively.

Transmission electron microscope ( Transmission electron microscope , TEM ) analysis

20 占 퐇 of the peptide nanostructure was dropped on a copper mesh coated with 200 mesh carbon and dried for 5 minutes. The remaining solvent was removed using filter paper, and the peptide nanostructure was stained with 2% Uranyl acetate dyeing reagent (Electron Microscopy Sciences). The grid was then placed in a desiccator to remove even moisture. And a peptide nanostructure was confirmed using an 80 kV transmission electron microscope (JEOL, JEM-1010).

Fluorescence image ( Fluorescence imaging ) Shooting

In order to stain the peptide nanostructure with thiopeptide and confirm with an optical microscope, 2 mM peptide was dissolved in a 20 mM HEPES buffer solution (pH 7.4) at 90 DEG C for 30 minutes, and 250 μM of thiopurine was added thereto. The peptide nanostructure was dropped on the glass surface to form a two-dimensional structure at the interface. The peptide nanostructure was transferred to a clean glass surface and then placed in a desiccator for 2 hours to remove water. Fluorescence-stained peptide nanostructures were confirmed by excitation at 430 ± 10 nm on a fluorescence microscope (Deltavision RT (Applied Precision, USA) microscope, Olympus IX70 camera).

computer modelling  Research

Computer predictive simulation of all peptide nanostructures was predicted using the Discovery Studio program (Version 3.1, Accelrys Inc., San Diego, Calif.). Each environment was measured by a molecular behavior predictor in a Discovery Studio program called CHARMm (Chemistry at Harvard Macromolecular Mechanics). Peptide molecular structure was heated and stabilized at 0.001 ps for 10 ps at 5-1,000 ° K.

MALDI - TOF  Mass spectrometry

10 mg of 2,5-dihydroxybenzoic acid was dissolved in 1 ml of a solvent in which ion-free water and acetonitrile containing 0.1% trifluoroacetic acid were mixed in a ratio of 3: 7. The peptide solution (1 mM, 0.5 ㎕) was dropped on a Maltitof plate, and 20 mM dithiothreitol (DTT) (20 mM, 0.5)) and ammonia water (8 mM, 0.5 ㎕) . All results were obtained using an Autoflex MALDI-TOF mass spectrometer (Bruker Daltonics), Smartbeam laser, and FlexControl software (Bruker Daltonics).

ESI ( Electrospray ionization ) Mass spectrometric analysis

The peptide two-dimensional structure was dissolved in methanol containing 0.5% acetic acid and purified by high performance liquid chromatography electrospray ionization mass spectrometry (Thermo-Finnigan LCQ deca XP MS ESI-MS), Phenomenex C4 reverse-phase column , 100 3 mm)) for 10 minutes, and the molecular weight of acetonitrile was measured.

X-ray diffraction  ( XRD ) analysis

Peptide nanostructures (1 mM, 1 ml) were formed on the glass surface at the air / water interface, transferred to a silicon wafer, and dried for 24 hours. (Resolution: 4,000 cm ^-1 ) at 300 cm ^{- 1} using an infrared measuring device (Thermo Nicolet 6700 FT-IR spectrometer, ATR accessory) to identify the chemical bonding state and pi bonding of the peptide nanostructure. 1.93 cm < ^-1 >).

FT - IR  ( Fourier transform infrared ) Spectroscopic analysis

Peptide nanostructures (1 mM, 1 ml) were formed on the glass surface at the air / solution interface, transferred to a silicon wafer and allowed to dry for 24 hours. Chemical binding of the peptide after the nanostructure state and pi-infrared measurement equipment to determine the pi bond (Thermo Nicolet 6700 FT-IR spectrometer , attenuated total reflection (ATR) accessory) 300 cm by using ^{from 1} 4,000 cm ^-1 ( resolution, 1.93 cm ^-1 ) was measured by 8 repetitive scans.

Raman Spectroscopy

Peptide nanostructures (1 mM, 1 ml) were formed on the glass surface at the air / water interface, transferred to gold-coated silicon wafers and dried for 24 hours. The measurement range of 200 cm ^{- 1} to 3000 cm ^{- 1} was then measured for 300 seconds in a Raman analyzer (Horiba Jobin-Yvon / LabRam Aramis Raman spectrometer (diode laser 785 nm, power = 1 mW)).

Example  One Peptides  synthesis

The peptide was synthesized with 2-chlorotrityl chloride (CTC) resin (1.26 mmol / g) using the Fmoc / tBu method. After the first amino acid was loaded (0.3-0.5 mmol / g), each coupling step consisted of 2 equivalents of Fmoc-amino acid, 2 equivalents of HBTU, 2 equivalents of HOBt and 4 equivalents of DIPEA, For two hours. The solvent was DCM and DMF in a ratio of 1: 1. The Fmoc group was removed by reaction with 20% piperidine / DMF for 20 min. The final peptide synthesized was cleaved in CTC resin by reaction with 93% TFA, 2% TIPS, 2% DODT and 3% The cut mixture was then filtered, washed with DCM and methanol, and the filtrate was concentrated in vacuo. The resulting residue was precipitated with cold (<10 ° C) diethyl ether, then centrifuged and vacuum dried. Peptides were purified, if necessary, by reversed phase HPLC and confirmed by MALDI TOF and ESI mass spectrometry. The purity of all synthesized peptides was over 95%.

1-1 Tyr - Tyr - Cys - Tyr - Tyr  ( YYCYY ) synthesis

Basically, the peptide synthesis proceeded as described above. 2 ml of 2-CTC resin (substitution ratio: 1.41 mmol / g), 459.54 mg (1 mmol) of tyrosine derivative Fmoc-Tyr (tBu) -OH and 60 ml of DMF were added and mixed well. Lt; / RTI &gt; The resin was filtered, and the resin was washed three times with DMF and MC. The resin was then washed three times with DMF, MC, and methanol sequentially. Fmoc titration revealed that the desired amino acid was introduced into the resin.

50 ml of 20% piperidine / DMF solution was added to the supernatant containing 2 g of the resin obtained above, and the mixture was allowed to react for 30 minutes. After three washes with DMF, MC, and methanol, the positive results of the Kaiser test confirmed that the Fmoc was lost. To 2 g of the obtained resin, 919.08 mg (2 mmol) of Fmoc-Tyr (tBu) -OH, 270.2 mg (2 mmol) of HOBt and 758.5 mg (2 mmol) of HBTU were added and then 60 ml of DMF was added. 662 [mu] l (4 mmol) of DIEA was added thereto and stirred for 2 hours. After the reaction, the resin was washed three times with DMF, MC, and methanol, and the reaction was terminated by negative results of the Kaiser test. The resin was then treated with 20% piperidine / DMF for 30 minutes to remove Fmoc.

Cysteine was bound and washed using 1171.4 mg (2 mmol) of Fmoc-Cys (Trt) -OH, 270.2 mg (2 mmol) of HOBt, 758.5 mg (2 mmol) of HBTU and 662 μl (4 mmol) of DIEA. The resin thus obtained was treated with 20% piperidine / DMF to remove Fmoc, and the Fmoc-Tyr (tBu) -OH was sequentially coupled twice in the same manner as described above. Then, 20% piperidine (TBu) -Tyr (tBu) -Cys (Trt) -Tyr (tBu) -Tyr (tBu) -CTC resin.

Tyr-Tyr-Cys-Tyr-Tyr was recovered from the polymer scaffold as follows. Trifluoroacetate in resin: anisole: (triisopropylsilane: 3,6-dioxa-1,8-octanedithiol (93: 3: 2: 2) After removing the protecting group of the side chain and separating the peptide from the resin, the resin was filtered out, the resin was washed with MC and methanol, and the filtrate was collected. The reaction mixture was concentrated, the cold diethyl ether was added to the concentrate, and the residue was placed in a freezer to maximize the amount of precipitate. The precipitate was filtered, washed with diethyl ether four times using a centrifugal separator, The dried peptide in solid form was obtained in 85% yield.

1-2 Tyr - Tyr - Ala - Cys - Ala - Tyr - Tyr  ( YYACAYY ) synthesis

622.68 mg (2 mmol) of Fmoc-Ala-OH, 270.2 mg (2 mmol) of HOBt and 758.5 mg (2 mmol) of HBTU were added to 2 g of the Tyr (tBu) -Tyr (tBu) -CTC resin obtained in Example 1-1 And dissolved in 60 ml of DMF. 662 [mu] l (4 mmol) of DIEA was added thereto and stirred for 2 hours. After the reaction, the resin was washed three times with DMF, MC, and methanol, and the reaction was terminated by the negative result of the Kaiser test. The resin was then treated with 20% piperidine / DMF for 30 minutes to remove Fmoc.

Cysteine was coupled with 1171.44 mg (2 mmol) of Fmoc-Cys (Trt) -OH, 270.2 mg (2 mmol) of HOBt, 758.5 mg (2 mmol) of HBTU and 662 μl And washed. The resin thus obtained was treated with 20% piperidine / DMF as described above to obtain Cys (Trt) -Ala-Tyr (tBu) -Tyr (tBu) -CTC resin.

Tyr (tBu) -Try (tBu) -Ala-Cys (Trt) -Ala-Tyr (tBu) -Tyr (tBu) -CTC resin was obtained by sequential coupling of alanine and tyrosine. Tyr-Tyr-Ala-Cys-Ala-Tyr-Tyr was recovered from the polymer scaffold by the method of Example 1-1 to obtain the title peptide in 80% yield.

Example  2 of various sequences Peptides  Formation of nanostructures under various conditions

2-1 YYCYY  And YYACAYY Peptides  Formation of nanostructures using

2-1-1 Formation of nanostructure on glass slide

0.5 mg, 1 mg, 1.5 mg and 2 mg of each of the peptides of the YYCYY and YYACAYY sequences obtained in Example 1 were dissolved in 50 mM phosphate buffer (pH 7.4) or HEPES buffer (pH 7.4) (4- (2 -hydroxyethyl) -1-piperazine ethane sulfonic acid, pH 7.4) and dissolved at 90 ° C. 10 μl, 20 μl, 40 μl, 60 μl, 80 μl, and 100 μl were dropped onto the glass surface in a unit of 25 μl in a constant-humidity atmosphere to form a nanostructure on the water and air interface And Fig. 2).

2-1-2 Petri dish ( petridish ) Formation of nanostructures on top

40 mg of each peptide of the above sequence was added to 20 ml of 50 mM phosphate buffer (pH 7.4) or HEPES buffer (pH 7.4) and dissolved at 90 ° C. Thereafter, the solution was poured into a Petri dish and allowed to stand at 25 ° C in a constant humidity environment to form a nanostructure having a flat surface between water and the atmosphere on the entire surface of the Petri dish (see FIG. 1D).

2-1-3 metal ion Added Peptides  Manufacture of nanostructures

After adding 1 equivalent of iron chloride, zinc chloride, cobalt chloride, cobalt nitrate, cobalt hydrate, manganese hydroxide, or lithium hydroxide to 0.5 mg, 1 mg, 1.5 mg and 2 mg of each of the above peptides, 50 mM phosphate buffer ) Or 1 ml of HEPES buffer (pH 7.4) was added and dissolved at 90 ° C. Subsequently, 10 μl of each solution, 20 μl, 40 μl, 60 μl, 80 μl, and 100 μl was dropped on a glass surface and allowed to stand at 25 ° C under a constant humidity atmosphere. As a result, Or more.

The results indicate that the addition of metal ions such as zinc, iron, cobalt, etc., can promote the formation of nanostructures due to their interaction with the peptide (results not shown).

2-2 Various Peptides  And Derivatives for the Formation of Nanostructures

The peptides of various sequences in Table 1 were synthesized in the same manner as in Example 1, and each of these peptides was dissolved in 50 mM HEPES (pH 7.4) to a final concentration of 1.1 mM. Next, 80 [mu] l of each solution was examined for the formation of nanostructures as in Example 2-1. The results are shown in Table 1. As shown in the following Table 1, when one or more tyrosines and one or more nucleophiles, cysteine, were bonded, it was confirmed that solid and flat solid nanostructures were well formed. In addition, when a tyrosine derivative (a dopa having one hydroxyl group at the meta position of tyrosine) was used, it was confirmed that a nanostructure was formed on the surface.

In Table 1, the flat surface formation was measured at a room temperature until the diameter reached 2 mm, very fast: formation in 1 minute, fast: 1 to 30 minutes, slow: 30 to 60 minutes, very slow: 60 minutes or more.

Example  3 formed Peptides  Characterization of nanostructures

3-1 Atomic force microscope  ( AFM Surface analysis of nanostructures

Each of the peptides YYACAYY and YYCYY obtained in Example 1 was dissolved to a concentration of 2 mM with 50 mM HEPES pH 7.2 buffer. This solution was completely dissolved through sonication (20 minutes) and heat treatment (80 ° C, 20 minutes). 100 μl of this solution was dropped onto the glass surface and allowed to stand at 25 ° C in a constant humidity atmosphere to induce peptide nanostructure formation on the interface. The surface-cleaned mica was transferred over the peptide nanostructure and allowed to dry for 5 minutes in air. The prepared samples were analyzed by AFM (see Figures 8-10).

Through AFM analysis, the self-assembling phenomenon of the nanostructure is specifically observed, and the self-assembly shape, the relationship between the fault layers, and the thickness or height of a single layer can be known.

FIG. 8A shows a relationship between a single layer formed by partially removing a portion of a peptide nanostructure having a stacked layered structure by using a cellophane tape, and FIG. 9 is a cross-sectional view of a portion of the nanostructure as a cellophane tape And the thickness or height of a single nanostructure was measured through a section obtained by removing the nanostructure.

As a result of the AFM analysis, it was confirmed that the peptide nanostructure has a typical supramolecular structure resulting from self-assembly phenomenon. Specifically, it was confirmed that a thin layer of about 1.4 nm, which corresponds to the height of the YYCYY molecular monomer, was formed on the interface with the layer repeatedly layered repeatedly (see FIGS. 8 to 10). Such a regular arrangement of thin layers repeatedly accumulates, which is expected to be the driving force for water to overcome the strong surface tension seen at the interface with air and to form a flat surface where the nanostructures are visible.

3-2 Through fluorescent dye staining Peptides  Characterization of nanostructures

3-2-1 Nile Red  ( Nile Red ) dyeing

Peptide nanostructures were stained with nile red that specifically reacted to hydrophobic environments. 2 mg / ml (2.2 mM) YYCYY, 0.2 mg / ml nile red was prepared by dissolving in 50 mM Hepes buffer pH 7.2 containing 5% DMSO. 100 μl of this solution was dropped on the glass surface in a drop form and allowed to stand at 25 ° C in a constant humidity atmosphere to induce peptide nanostructure formation on the air / water interface. The formed peptide nanostructure was transferred to a cleaned surface of the glass surface and observed with a fluorescence microscope (see FIG. 3A).

Fluorescent coloring reagents used for fluorescence microscopy were Nile red fluorescent coloring reagents that fluoresce well and bind well to hydrophobic groups. As shown in FIG. 3A, it can be confirmed that the formed nanostructure is a peptide containing at least one tyrosine having a hydrophobic property.

3-2-2 Thiopurine  ( Thoiflavin -T, ThT ) dyeing

In general, fluorescence analysis was performed using thioflavin T (ThT), which fluoresces by being inserted between peptide nanostructures. 1 mg / ml YYCYY dissolved in 50 mM Hepes buffer pH 7.2 was reacted with 50 μM ThT. 100 μl of this solution was dropped on the glass surface in a drop form and allowed to stand at 25 ° C in a constant humidity atmosphere to induce peptide nanostructure formation on the interface. The formed peptide nanostructure was transferred to a cleaned glass surface and observed with a fluorescence microscope (see FIG. 3).

As shown in FIGS. 3B and 3C, it was confirmed that the peptide was one containing at least one tyrosine in which the nanostructure was formed.

Example  4 formed Peptides  Analysis of self-repairing properties of nanostructures

In the peptide nanostructure formed in Example 2, defects were formed on the surface using sharp tweezers, and self-complementary complementary properties by intermolecular self-assembly were analyzed. The prepared peptide nanostructure was found to have an ability to actively react to damage caused by external stimuli and to immediately heal the defect (see FIG. 18B). This means that the self-healing system allows for immediate self-repair of some damage to the nanostructure.

Therefore, it will be suitable for a scratch-resistant nanostructure, and when a specific molecule having a very important function is encapsulated with the nanostructure according to the present invention, it can be applied to a storage and delivery system of a specific drug by storing the drug well .

Example  5 formed Peptides  Transition of the nanostructure over the secondary substrate

Transition techniques on various substrates are needed for high applicability of peptide nanostructures formed on the interface. The present inventors have found that, in addition to a method of transferring a peptide substrate having a clear surface treated with the peptide nanostructure obtained in Example 2 above a peptide nanostructure, a secondary substrate is previously placed in the peptide solution for more stable nanostructure transfer, (See Figs. 1 and 19). The nanostructure is naturally transferred onto the secondary substrate according to the reduction of the total volume of the solution.

This is a new immersion coating method that can replace gravure coating, Meyer bar coating, or spin coating, which are widely used. In other words, it means that the nanostructure can be applied to the substrate without specific equipment. In this way, the use of expensive coating equipment and the problems of complex coating processes can be solved.

Example  6 YACAYY Peptides  And To polypyrrole  The conductive polymer film

Pyrrole (or aniline, thiophene or 3,4-ethylenedioxythiophene) and YYACAYY peptide (2 mM) were mixed in 1 ml of 50 mM HEPES at a 1: 1 molar ratio, and 100 μl of the mixture was used as in Example 2 As a result of forming the nanostructure, a flat surface was formed after 10 minutes. That is, a two-dimensional nanostructure was formed at the interface between the solution and air. Aniline, thiophene, or pyrrole trapped between the peptide two-dimensional structures by using ammonium peroxide or iron (III) chloride (2 molar equivalents relative to the monomer) as an oxidizing agent on the pyrrole-containing hybrid flat surface formed at the interface of the air and the solution The 3,4-ethylenedioxythiophene molecule was polymerized as a conductive polymer having a two-dimensional structure. As a result, a well-ordered crystal structure was formed (see Fig. 20). As a result of AFM analysis, the thickness was 5 nm, and as a result of a high-power TEM analysis, it was confirmed that the crystal had a hexagonal structure with a = 0.445 nm (Fig. 20C, D). These results indicate that the metallicity of the polymer film can be increased due to the regular arrangement as described above.

It will be understood by those skilled in the art that the foregoing description of the present invention is for illustrative purposes only and that those of ordinary skill in the art can readily understand that various changes and modifications may be made without departing from the spirit or essential characteristics of the present invention. will be. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive.

Claims (32)

A compound of formula 1:
X ¹ a-Y n -X ² b
In the above formula
X ¹ and X ² are each independently a D- or L-type natural or unnatural amino acid or a derivative thereof having a side chain capable of pi-phi interactions, X ¹ and X ² are the same or different,
Y is a D- or L-type natural or unnatural amino acid or derivative thereof having charged side chains or nucleophilic side chains capable of forming a bridge,
a and b are the same or different integers from 1 to 10,
n is an integer of 1 to 10; The compound of formula (1) according to claim 1, wherein the crosslinking comprises covalent bonding or coordinate bonding by metal. 3. The pharmaceutical composition according to claim 2, wherein the amino acid capable of coordinating with the metal is cysteine, homocysteine, penicillamine, salenocysteine, histidine, lysine, ornithine, aspartic acid, glutamic acid, asparagine or glutamine. compound. 2. The compound of formula (I) according to claim 1, wherein the amino acid capable of pi-pi interactions is an amino acid having an aromatic side chain. 2. The compound of claim 1, wherein the amino acid capable of pi-pi interactions is phenylalanine, tryptophan or tyrosine. The compound of formula (I) according to claim 1, wherein the amino acid capable of forming the crosslinking is an amino acid having an SH residue. 2. The method of claim 1, wherein X ¹ X ² a and b are sequences that are the same, or has the amino acid sequence of the left and right symmetrical with each other in the center of the Y, the compounds of formula (I). The compound of formula (I) according to claim 1, wherein n is 1, and a and b are each an integer of 2 to 5. 2. The compound of formula (I) according to claim 1, wherein n is 1, and a and b are the same as each other. The compound of claim 1, wherein the compound of formula (1) is selected from the group consisting of YYCYY, YYYCYYY, YYACAYY, YYAACAAYY, YYGCGYY, YFCFY, FYCYF, FFCFF, YYAKAYY, YYAEAYY, CYY, YY, YYY, YYYY, YKCKYY, YYECEYY, YYDCDYY, YYAHAYY, YYHYY, &Lt; / RTI &gt; YYAPAYY, YYPYY and derivatives thereof. 10. A self-assembled nanostructure comprising a compound according to any one of claims 1 to 10. 11. The self-assembled nanostructure of claim 10, wherein the self-assembled nanostructure comprises a film, nanofiber, or sphere. 13. The self-assembled nanostructure of claim 12, wherein the film is planar or facing. 14. The self-assembled nanostructure according to claim 13, wherein the planar surface or the facing surface has a multilayer structure. 12. The self-assembled nanostructure according to claim 11, wherein the self-assembled nanostructure is a flat surface, and the compound of Formula 1 is contained at a concentration of about 0.1 to 10 mM or more. 16. The self-assembled nanostructure of claim 15 wherein the compound of Formula 1 is included at a concentration of about 0.22 mM. 12. The self-assembled nanostructure according to claim 11, wherein the self-assembled nanostructure is a nanofiber, and the compound of the formula (1) is contained in an amount of about 0.1 to 10 mM. 18. The self-assembled nanostructure of claim 17 wherein the compound of Formula 1 is included at a concentration of at least about 0.33 mM. 12. The self-assembled nanostructure according to claim 11, wherein the self-assembled nanostructure is formed on a bulk of a liquid-gas interface or a liquid-liquid. 20. The method of claim 19 wherein the liquid at the liquid-gas interface is a volatile or non-volatile hydrophobic or hydrophilic solvent and the gas is air, nitrogen, helium, hydrogen, carbon monoxide, or carbon dioxide, Wherein the liquid is a volatile or non-volatile hydrophobic or hydrophilic solvent. 21. The method of claim 20, wherein the volatile or nonvolatile hydrophobic or hydrophilic solvent is selected from the group consisting of water, alcohols, hydrocarbons including halogens, dimethylsulfoxide, dimethylformamide, dimethylformacetamide, N-methylpyrrolidone, Wherein the bioactive agent is selected from the group consisting of hydrochloric acid, hydrobromic acid, hydrobromic acid, hydrobromic acid, hydrobromic acid, hydrobromic acid, hydrobromic acid, hydrobromic acid, 20. The self-assembled nanostructure of claim 19, wherein the bulk phase is formed at a hydrophilic and hydrophobic liquid interface. 12. The self-assembled nanostructure according to claim 11, wherein the self-assembled nanostructure is formed at a pH of from 3 to 8 including a compound isoelectric point of Formula (1) contained in the nanostructure. 13. The self-assembled nanostructure of claim 12, wherein the film structure is formed at a liquid-gas interface, and wherein the nanofibers are formed on a liquid or liquid-liquid bulk. 12. The self-assembled nanostructure of claim 11, wherein the self-assembled nanostructure further comprises a monomer. 26. The self-assembled nanostructure of claim 25, wherein the monomer is pyrrole, aniline, thiophene, or 3,4-ethylenedioxythiophene. A conductive polymer film comprising a compound of formula (I) and a monomer. A method for producing a conductive polymer film using the compound of formula (1), comprising reacting a compound of formula (1) with a monomer under conditions favoring the formation of a self-assembled nanostructure. A method for forming a self-assembled nanostructure using the compound of formula (1), comprising the step of reacting the compound of formula (1) under conditions favoring the formation of the self-assembled nanostructure. 31. The method of claim 29, wherein the favorable conditions for forming the self-assembled nanostructure comprises: reacting the compound of Formula 1 at a concentration of at least 0.2 mM on a bulk-liquid interface or liquid-liquid bulk, in an oxidizing atmosphere, Wherein the reaction is carried out at a pH that includes the isoelectric point of the nanocomposite. 31. The method of claim 30, wherein the self-assembled nanostructure is a film or nanofiber structure, the film is formed at a liquid-gas interface, and the nanofiber structure is formed on a bulk of a liquid or liquid- Method of forming nanostructure. 32. The method of claim 31, wherein the method further comprises adding a metal ion to the compound of Formula 1.

Images