Surfactant containing branched hydrophobic chains with amino acid residues at the branching point

Abstract

The invention relates to the fields of colloidal chemistry and medicinal chemistry. A surfactant containing branched hydrophobic chains with amino acid residues at the branching point is characterized by general formula (I), where R1-A-R2 represents an amino acid residue; k can be equal to 1, 2 or 3; l can be equal to 3, 4, 5, 6 or 7; the amino acid residue has an L configuration; R1 and R2 are the same or different residues from the list shown; m is an integer from 4 to 13. New compounds are obtained which provide for better binding of molecules inside lipid nanoparticles (LNPs), as well as more uniform packing of molecules inside LNPs, without the formation of ordered phases such as a lamellar phase.

Description

A surfactant containing branched hydrophobic chains with amino acid residues at the branching point

[0001] The present invention relates to the fields of colloid chemistry and medicinal chemistry, in particular to the structure of substances that are components of compositions of surfactants and / or lipids, compositions of natural and / or synthetic lipids and compositions of polymers with additives of surfactants and / or lipids.

[0002] Compositions based on surfactants, natural and synthetic lipids, and polymer-based compositions with added surfactants and / or lipids (hereinafter referred to as Lipid Compositions) are used in various technical fields. In addition to the trivial use of lipid compositions to reduce surface tension, they are used to solubilize both low- and high-molecular-weight drugs, including ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) molecules. Lipid Compositions, whether empty (without drugs) or loaded with drugs or nucleic acids, can be prepared such that they form a suspension of particles in water or aqueous buffer solutions. These particles are called lipid nanoparticles (LNPs) and have characteristic sizes ranging from a few nanometers to several thousand nanometers.In fact, LNPs are used as auxiliary agents in the preparation of pharmaceuticals. They serve as carriers for therapeutic agents: low-molecular-weight substances, proteins, and nucleic acids.

[0003] The components of LNP include surfactants, natural and synthetic lipids, fatty acids, triglycerides, cholesterol, and synthetic derivatives such as polyethyleneglycol lipids. The ability of LNP to perform its function depends on the structure of the components included in the LNP, their ratio, and the method of LNP production.

[0004] Thus, cationic lipids are used to bind nucleic acids, cholesterol, triglycerides and phospholipids are used as structural fillers, and polyethyleneglycol lipids are used as stabilizers of the resulting particles.

[0005] LNPs are formed in an aqueous solution, and the LNP components are held together by intermolecular interactions, both hydrophobic and polar. The lipid and synthetic components of LNPs have a classic surfactant structure with a polar head and one or two hydrophobic tails. The hydrophobic tails can be branched. This, on the one hand, increases the hydrophobic surface area of ​​the molecule, and on the other, prevents the packing of hydrophobic chains into ordered clusters (parallel packing of chains in all-trans configurations). Polar interactions within LNPs are possible between the polar heads of the molecules. This can lead to ionic interactions between the negatively charged phosphate groups of phospholipids and the positively charged groups of cationic lipids, as well as hydrogen bonds between hydroxyl-containing components of LNPs, for example, between cholesterol and lysophosphatidylcholine.Together, hydrophobic and polar intermolecular interactions determine the internal structure of LNPs.

[0006] In accordance with the present invention, a structure of lipid composition components is proposed that leads to the simultaneous branching of the hydrophobic chain and the introduction of polar groups capable of forming intermolecular bonds into the hydrophobic chain.

[0007] The technical result of the claimed invention is an improvement in the binding of molecules within lipid nanoparticles, as well as a generally more uniform packing of molecules within LNPs in comparison with lipid compositions without the use of the present invention.

[0008] The present invention relates to the fields of colloid chemistry and medicinal chemistry, in particular to the structure of substances that are components of lipid compositions. Specifically, the present invention is a substance containing branched hydrophobic chains, the branching of which utilizes amino acid residues, and said substance is characterized by the general formula:

[0009]

[0010] Where:

[0011]

[0012] k can be equal to 1, 2 or 3;

[0013] l can be equal to 3, 4, 5, 6 or 7.

[0014] The amino acid residue is in the L-configuration.

[0015] According to the structure of the amino acid residue, R1 and R2 are the same or different residues from the following list:

[0016]

[0017] m is an integer between 4 and 13.

[0018] By simultaneously using chain branching and incorporating amide groups into the midchain, improved molecular binding within the lipid nanoparticles is achieved, and ordered phases such as lamellar phases are prevented. Overall, the molecular packing within the LNPs is more uniform compared to lipid compositions not using the present invention.

[0019] The essence of the claimed invention is explained by a detailed description, examples and figures, which depict:

[0020] 31 P NMR spectrum of liposomes (left) and micelles (right).

[0021] A fragment of the IR spectrum of liposomes from egg phosphatidylcholine, the vibration range of the phosphate group, decomposed into components.

[0022] Scheme of synthesis of 2-hydroxyethyl-(bis-{5-[1,4-dioctyl-butanedioate-2-yl]carbamoyl})pentyl-amine (ASP-268).

[0023] TEM image (left), its analysis results (top right) and DLS data (bottom right) for ASP-268-based LNPs.

[0024] Scheme of synthesis of 4-hydroxybutyl (bis-{-5-[-decanyl-4-methyl-pentanoyl-2-yl]-carbamoyl pentyl}) amine (Leu-4610).

[0025] TEM image (left), its analysis results (top right) and DLS data (bottom right) for Leu-4610-based LNPs.

[0026] Scheme of synthesis of 2-hydroxybutyl-(bis-{5-[1,5-dioctyl-pentanedioate-2-yl]carbamoyl}-pentyl)-amine (Glu-468).

[0027] TEM image (left), its analysis results (upper right) and DLS data (lower right) for Glu-468-based LNPs.

[0028] Scheme for the synthesis of 2-hydroxyethyl-(bis-{5-[1,5-di-N-octyl-pentanediamid-2-yl]carbamoyl}-heptyl)-amine (Gln-288).

[0029] TEM image (left), its analysis results (upper right) and DLS data (lower right) for Gln-288-based LNPs.

[0030] Scheme of synthesis of 4-hydroxybutyl-(bis-[octyl-3-{4-hexyloxyphenyl}-propanoate-2-yl-carbamoyl]-pentyl)-amine (Tyr-4686).

[0031] TEM image (left), its analysis results (upper right) and DLS data (lower right) for Tyr-4686-based LNPs.

[0032] Methods, materials and software.

[0033] Chemical synthesis.

[0034] Reagents of chemically pure grade or equivalent were used. Solvents were distilled before use and, if necessary, dried using standard methods. A standard set of chemical glassware was used. Reactions were carried out in round-bottomed flasks with magnetic stirrers. Unless otherwise stated, reactions were carried out at room temperature. Reactions were carried out under an inert atmosphere. Column chromatography on silica gel 90 (pore size 63-200 μm) was used to isolate the final and intermediate products.

[0035] Obtaining LNC:

[0036] Lipid solutions in ethanol or chloroform were mixed in a round-bottomed flask. The solvent was removed on a rotary evaporator under vacuum with a water-jet pump at a bath temperature of 25-30°C. The resulting lipid film was dried under vacuum at 50 µHg for three hours. Water or phosphate buffer was then added. The lipid film was hydrated for 1 hour. The sample was then sonicated for 10-15 minutes.

[0037] Transmission electron microscopy (TEM).

[0038] The morphology of LNPs was studied using a Zeiss LIBRA®120 PLUS transmission electron microscope (Germany) with an accelerating voltage of 80 kV. Samples were obtained by applying the lipid suspension to be studied (15-20 μl of 0.3 mM or 1 mM) to a carbon-coated copper grid, followed by negative staining with uranyl acetate (15-20 μl of a 2% aqueous solution). Two minutes after each addition, excess liquid was carefully removed with a corner of filter paper.

[0039] Laser dynamic light scattering (DLS).

[0040] Measurements of the hydrodynamic diameter of self-assembled lipid particles were carried out using a Brookhaven 90Plus NanoParticle Size Distribution Analyzer (USA).

[0041] All samples were analyzed with the following instrument settings: temperature 25°C; solvent water, viscosity 0.890 cP; refractive index of solvent 1.330; refractive index of particles 1.440; angle 90.00°; number of repeated measurements 5, time of one measurement 1 min. Measurements were performed in disposable plastic cuvettes (Sardsted, Germany), sample volume 2 ml, concentration of cationic lipid 5 μM.

[0042] TEM image analysis.

[0043] ImageJ software was used to analyze TEM images.

[0044] The LNP image analysis was conducted in several stages. First, from the array of obtained images, those were selected in which the particles appeared most contrasting within the image field and were present in sufficient quantities. Individual particles were then isolated from these electron micrographs. The Feret diameter—the greatest distance between two points within the selected area—was determined for each particle. The combined array of particle diameter values ​​from a single image formed a size distribution for each monocationic amphiphile suspension, which was compared with the DLS data.

[0045] 31 P NMR Spectroscopy.

[0046] Samples were prepared using deuterium hydroxide (D2O). 31P NMR spectra were recorded on a DRX 500 spectrometer (Bruker, Germany) at 202.5 MHz using a high-resolution, broadband probe with a diameter of 5 mm. A Hahn echo pulse sequence and broadband decoupling were used during data acquisition. 31 P–1H. Before Fourier transform, the FID was multiplied by a Lorentz function with a spreading factor of 5 Hz. All spectra contained 4096 complex data points. Spectra were recorded at 297 K.

[0047] The narrow peak shown in Fig. 1 indicates that there are no distinct directions in the lipid packing (all rotation directions are equivalent). The broad, complex peak indicates that the lipids form aggregates with different axial sizes, such as a lamellar phase. The signal anisotropy is described by the parameter The less , the more isotropic the signal on the spectrum 31P, and the more uniformly the phospholipid molecules are packed. For liposomes made from distearoylphosphatidylcholine (anisotropic signal) = 43.1 ± 3.0 ppm.

[0048] Fourier transform infrared spectroscopy.

[0049] ATR-FTIR spectra were recorded using a Bruker Tensor 27 spectrometer equipped with a liquid nitrogen-cooled mercury cadmium telluride (MCT) detector. Samples were placed in a BioATR-II temperature-controlled cell with a ZnSe ATR element (Bruker, Germany). The ATR-FTIR spectrometer was purged with a constant flow of dry air. ATR-FTIR spectra were recorded in the range from 900 to 3000 cm-1. For each spectrum, 70 scans were accumulated at a scan rate of 20 kHz and averaged. All spectra were recorded in K2HPO4, 1 mM; KH2PO4– 1 mM; KCl, 10 mM, pH 7.0, temperature 23 °C, lipid concentration of 20 mg / mL, application volume of 40 μL to the ZnSe element. The experiment was repeated three times.

[0050] Spectral data were processed using Opus 7.5 software (Bruker, Germany), which includes linear blank subtraction, linear baseline correction, and atmospheric compensation. Savitzky-Golay smoothing was used to remove white noise when necessary, and broad peaks were deconvolved. Peaks were identified using Bruker's standard peak selection procedure.

[0051] In the region of 1100-1300 cm -1 the main peak in the IR spectrum of lipid particles is the asymmetric stretching vibration of the PO2 group (A, ~1225 cm -1 ), and its shoulder is the asymmetric stretching vibration of the PO bond (B, ~1177 cm -1 ). (see ). The change in the position of the peak of component A is associated with the formation of hydrogen bonds. For pure phosphatidylcholine, the position of peak A is 1229 cm -1 Due to structural features, there are no hydrogen bonds between lipids in pure phosphatidylcholine systems.

[0052] Example 1.

[0053] Asp-268.

[0054] 2-hydroxyethyl-(bis-{5-[1,4-dioctyl-butanedioate-2-yl]carbamoyl}-pentyl)-amine (ASP-268)

[0055] [Structure of Asp-268]

[0056] Synthesis of Asp-268.

[0057] In example 1, k=1, l=5, R1 = CH3-(CH2)7-OCOCH2-*, R2 = CH3-(CH2)7-* (m=7). The amino acid fragment is an aspartic acid residue. Designation: Asp-268.

[0058] The synthesis scheme of 2-hydroxyethyl-(bis-{5-[1,4-dioctyl-butanedioate-2-yl]carbamoyl})pentylamine (ASP-268) is shown in Fig. Condensation of two equivalents of octanol (1) with one equivalent of BOC-protected aspartic acid (2) under the action of dicyclohexylcarbodiimide (DCC) and dimethylaminopyridine (DMAP) in dry methylene chloride followed by deprotection of BOC with trifluoroacetic acid in methylene chloride afforded dioctyl aspartic acid (3). Acylation of dioctyl aspartic acid with w-chlorohexanoic acid (4) using DCC and DMAP afforded the trisubstituted aspartic acid derivative (5). Alkylation with the 5-ethanolamine derivative (6) in dimethylformamide over dry potassium carbonate gives the final product ASP-268.

[0059] ASP-268 1H NMR (400 MHz): δ 0.87 (t, 12H, J = 7.00), 1.14-1.62 (m, 52H), 1.64-1.82 (m, 8H), 2.22 (t, 4H J = (2.8H27), . t, J = 2.67 Hz), 2.99 (d, 4H, J = 6.26 Hz), 3.54 (2H, t, J = 2.67 Hz), 4.14–4.29 (m, 8H)), 5.01 (2H, dd, J = 6.26 , Hz).6.2. 13C NMR (101 MHz): δ 14.02 (4C), 22.63 (4C), 25.40 (2C), 25.82 (4C), 27.10 (4C), 29.26 (4C), 29.35 (8C), 31.75 (4C), 31.75 (4C), 49.50 (2C), 53.74 (2C), 57.00 (1C), 59.30 (1C), 65.17 (4C), 170.30 (2C), 171.90 (2C), 174.70 (2C). MS: M+ calculated 967.7436; found 967.7399.

[0060] Lipid composition and Asp-268-based LNC.

[0061] Analysis of a TEM image of an ASP-268 and egg phosphatidylcholine suspension (1:1 mol). Comparison of particle size distributions obtained using dynamic laser light scattering (DLS) and transmission electron microscopy (TEM) (see). A total of 46 particles are in the TEM image field. The resulting LNPs are dense particles. The chemical shift anisotropy is ~19 (see Table 1), which is more than two times smaller than the chemical shift anisotropy for liposomes from distaroylphosphatidylcholine. This means that the addition of ASP-268 to LNPs leads to the destruction of the lamellar phase and the formation of a more isotropic packing of lipid molecules. A shift in the peak of the phosphate group vibration band (Table 1) indicates the formation of hydrogen bonds between phospholipids.

[0062] [Table 1]. Characteristics of LNPs based on Asp-268. Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Asp-268100.4±15.9 nm19.3±1.4 ppm1221 cm -1

[0063] Example 2.

[0064] 4-hydroxybutyl (bis-{-5-[-decanyl-4-methyl-pentanoyl-2-yl]-carbamoyl pentyl}) amine (Leu-4610).

[0065] [Structure of Leu-4610]

[0066] In example 2 k=3, l=5, R1= (CH3)2-CH - CH2-*, R2= CH3-(CH2)9-* (m=9). A leucine residue is used as the amino acid fragment. Designation: Leu-4610.

[0067] Synthesis of Leu-4610.

[0068] The scheme of synthesis of 4-hydroxybutyl (bis-{-5-[-decanyl-4-methyl-pentanoyl-2-yl]-carbamoyl pentyl}) amine (Leu-4610) is shown in Fig. Condensation of leucine 1 and w-chlorohexanoic acid chloride 2 in dry pyridine at 0 °C led to amide 3, the condensation of which with decanol 4 under Steglich reaction conditions (condensing agent dicyclohexylcarbodiimide, base dimethylaminopyridine) gave derivative 5. Alkylation of butanolamine 6 with derivative 5 in dry dimethylformamide over dry potassium carbonate gave the desired Leu-4610.

[0069] 1H NMR (400 MHz): δ 0.80-0.96 (m, 18H), 1.14-1.86 (m, 54H)), 2.22 (t, 4H, J = 7.37 Hz), 2.71-2.83 (m, 6H), 3.34 (2H, t, J = 7.02 Hz), 4.14-4.36 (m, 6H)). 13C NMR (101 MHz): δ 14.02 (2C), 19.79 (1C), 22.57 (4C), 22.63 (2C), 24.38 (2C), 25.40 (2C), 25.82 (2C), 27.10 (2C), 27.20 (2C), 29.26 (2C), 29.40 (8C), 30.00 (1C), 31.75 (2C), 36.80 (2C), 40.94 (2C), 52.60 (2C), 53.74 (3C), 62.20 (1C), 65.17 (2C), 170.30 (2C), 174.70 (2C). MS: M+ calculated 823.7013; 823,6997 found.

[0070] Lipid composition and LNP based on Leu-4610.

[0071] TEM image analysis of a Leu-4610, distearoylphosphatidylcholine (DSPC), and cholesterol suspension (1 / 1 / 0.2 mol). Comparison of particle size distributions obtained using DLS and TEM. A total of 75 particles are present in the TEM image field (). The resulting LNPs are dense particles. The chemical shift anisotropy is ~21 (see Table 2), which is approximately half the chemical shift anisotropy of distearoylphosphatidylcholine liposomes. This means that the addition of Leu-4610 to LNPs disrupts the lamellar phase and promotes a more isotropic packing of lipid molecules. A shift in the peak of the phosphate group vibration band (Table 2) indicates the formation of hydrogen bonds between phospholipids.

[0072] [Table 2]. Characteristics of Leu-4610-based LNPs. Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Leu-4610112.5±13.8 nm21.2±1.9 ppm1222 cm -1

[0073] Example 3.

[0074] 2-hydroxybutyl-(bis-{5-[1,5-dioctyl-pentanedioate-2-yl]carbamoyl}-pentyl)-amine (Glu-468).

[0075] [Structure of Glu-468]

[0076] In example 3 k=3, l=5, R1 = CH3-(CH2)7-OCOCH 2- -CH2-*, R2 = CH3-(CH2)7-* (m=7). The amino acid residue used is a glutamic acid residue. Designation: Glu-468.

[0077] Synthesis of Glu-468.

[0078] The scheme of synthesis of 2-hydroxybutyl-(bis-{5-[1,5-dioctyl-pentanedioate-2-yl]carbamoyl}-pentyl)-amine (Glu-468) is presented in. Condensation of two equivalents of octanol 1 with one equivalent of Boc-glutamic acid 2 under the action of dicyclohexylcarbodiimide (DCC) and dimethylaminopyridine (DMAP) followed by deprotection of BOC-protection led to dioctylglutamic acid 3. Acylation of dioctylglutamic acid 3 with w-chlorohexanoic acid also under the action of dicyclohexylcarbodiimide and dimethylaminopyridine led to amide 5. Alkylation of butanolamine 6 with derivative 5 in dry dimethylformamide over anhydrous potassium carbonate gave the desired Glu-468.

[0079] 1H NMR (400 MHz): δ 0.87 (t, 12H, J = 7.00)), 1.14-2.01 (m, 68H), 2.22 (4H, t, J = 7.37 Hz), 2.40 (t, 4H, 2.40, J = 7.37 Hz), 2.71-2.83 (m, 6H)), 3.34 (2H, t, J = 7.02 Hz), 4.14-4.43 (m, 10H). 13C NMR (101 MHz): δ 14.02 (4C), 19.79 (1C), 22.63 (4C), 25.40 (2C), 25.82 (4C), 26.19 (2C), 27.10 (4C), 29.26 (4C), 29.40 (8C), 30.00 (1C), 31.14 (2C), 31.75 (4C), 36.80 (2C), 52.60 (2C), 53.74 (3C), 62.20 (1C), 65.17 (4C), 170.30 (2C), 173.00 (2C), 174.70 (2C). MS: M+ calculated 1023.8062; 1023,8011 found.

[0080] Lipid composition and LNP based on Glu-468.

[0081] Analysis of the TEM image of a Glu-468 suspension, distearoylphosphatidylcholine (DSPC) (1 / 1 mol). Comparison of particle size distributions obtained by DLS and TEM. A total of 135 particles are present in the TEM image field (see). The resulting LNPs are dense particles. The chemical shift anisotropy is ~14 (see Table 3), which is significantly (more than two times) smaller than the chemical shift anisotropy for liposomes from distearoylphosphatidylcholine. This means that the addition of Glu-468 to LNPs leads to the destruction of the lamellar phase and the formation of a more isotropic packing of lipid molecules. The shift of the peak of the phosphate group vibration band (Table 3) indicates the formation of hydrogen bonds between phospholipids.

[0082] [Table 3] Characteristics of Glu-468-based LNPs. Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Glu-46851.3±5.0 nm14.2±1.2 ppm1219 cm -1

[0083] Example 4.

[0084] 2-hydroxyethyl-(bis-{5-[1,5-di-N-octyl-pentanediamid-2-yl]carbamoyl}-heptyl)-amine (Gln-288)

[0085] [Structure of Gln-288]

[0086] In example 4 k=1, l=7, R1 = CH3-(CH2)7-NHCOCH 2- -CH2-*, R2 = CH3-(CH2)7-* (m=7). A glutamine residue is used as the amino acid fragment. Designation: Gln-288.

[0087] Synthesis of Gln-288.

[0088] The scheme of synthesis of 2-hydroxyethyl-(bis-{5-[1,5-di—N-octyl-pentanediamide-2-yl]carbamoyl}-heptyl)-amine (Gln-288) is presented in . Condensation of two equivalents of normal octylamine 1 with one equivalent of Boc-glutamic acid 2 under the action of dicyclohexylcarbodiimide (DCC) and dimethylaminopyridine (DMAP) followed by deprotection of BOC-protection led to dioctylglutamine 3. Acylation of dioctylglutamine 3 with w-chlorooctanoic acid also under the action of dicyclohexylcarbodiimide and dimethylaminopyridine led to amide 5. Alkylation of ethanolamine 6 with derivative 5 in dry dimethylformamide over anhydrous potassium carbonate gave the desired Gln 288.

[0089] 1H NMR (400 MHz): δ 0.87 (12H, t, J = 7.00), 1.14–1.65 (68H, m), 1.93 (4H, dd, J = 7.37, 7.37 Hz), 2.15–2.32 Hz (2.7 t, J = 7.4), 2.85 (2H, t, J = 2.67 Hz), 3.19 (8H, t, J = 7.37 Hz), 3.54 (2H, t, J = 2.67 Hz), 4.38 (2H, dd, J = 7.30, 7.30 Hz). 13C NMR (101 MHz): δ 14.02 (4C), 22.63 (4C), 25.40 (2C), 27.10 (10C), 29.40 (16C), 31.75 (4C), 32.90 (2C), 36.84 (2C), 36.49 (2C). (2C), 53.74 (2C), 57.00 (1C), 59.30 (1C), 171.60 (2C), 172.83 (2C), 174.70 (2C). MS: M+ calculated 1047.9014; found 1047.8997.

[0090] Lipid composition and Gln-288-based LNC.

[0091] Analysis of a TEM image of a Gln-288 suspension, egg phosphatidylcholine (1 / 1 mol). Comparison of particle size distributions obtained using DLS and TEM. A total of 79 particles (cm) are present in the TEM image field. They are dense particles with an average diameter of 84.4 ± 9.72. The chemical shift anisotropy is ~25 (see Table 4), which is approximately two times smaller than the chemical shift anisotropy for liposomes from distaroylphosphatidylcholine. This means that the addition of Leu-4610 to LNPs leads to the destruction of the lamellar phase and the formation of a more isotropic packing of lipid molecules. A shift in the peak of the phosphate group vibration band (Table 4) indicates the formation of hydrogen bonds between phospholipids.

[0092] [Table 4] Characteristics of Gln-288-based LNPs. Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Gln-28884.4±9.72 nm25.2±3.1 ppm1222 cm-1

[0093] Example 5.

[0094] 4-hydroxybutyl-(bis-[octyl-3-{4-hexyloxyphenyl}-propanoat-2-yl-carbamoyl]-pentyl)-amine (Tyr-4686).

[0095] [Structure of Tyr-4686]

[0096] In example 5, k=3, l=5, R1 = CH3-(CH2)5-(p-Ph)-CH2-*, R2 = CH3-(CH2)7-* (m=7). A tyrosine residue is used as the amino acid fragment. Designation: Tyr-4686.

[0097] Synthesis of Tyr-4686.

[0098] The scheme of synthesis of 4-hydroxybutyl-(bis-[octyl-3-{4-hexyloxyphenyl}-propanoate-2-yl-carbamoyl]-pentyl)-amine (Tyr-4686) is presented in. Steglich condensation (under the action of carbodiimide) of octanol 1 and BOC-protected tyrosine 2 gave ester 3. Condensation of derivative 3 with hexanol 4 in the presence of diisopropyl azidocarboxylate (DIAD) and thiphenylphosphine (PPh3) (Mitsunobu reaction) gave derivative 5. After removal of BOC-protection by the action of trifluoroacetic acid in methylene chloride and condensation with w-chlorohexanoic acid 6, derivative 5 was converted to amide 7. Alkylation of butanolamine 8 with derivative 7 in dry dimethylformamide over anhydrous potassium carbonate gave the desired Tyr-4686.

[0099] 1H NMR (400 MHz): δ 0.87 (12H, t, J = 7.00), 1.14-1.86 (52H, m), 2.22 (4H, t, J = 7.37), 2.37 (4H, t, J = 7.37), 2.71-2.89 (10H, m), 3.34 (2H, t, J = 7.02 Hz), 4.14-4.27 (4H, m), 4.70 (2H, dd, J = 6.86, 6.86 Hz), 7.05-7.20 (8H, m). 13C NMR (101 MHz): δ 14.07 (4C)), 19.79 (1C), 22.63 (4C), 24.82 (2C), 25.40 (2C), 25.82 (2C), 27.10 (4C), 29.26 (2C), 29.40 (4C), 30.00 (1C), 31.75 (4C), 33.88 (2C), 36.80 (2C), 38.20 (2C), 53.20 (2C), 53.74 (3C), 62.20 (1C), 65.17 (2C), 114.30 (4C), 130.00 (4C), 135.40 (2C), 150.60 (2C), 169.46 (2C), 170.30 (2C), 174.70 (2C). MS: M+ calculated 1063.7436; found 1063.7421.

[0100] Lipid composition and LNP based on Tyr-4686.

[0101] Analysis of the TEM image of a suspension of Tyr-4686, DSPC, cholesterol (1 / 1 / 0.1 mol). Comparison of particle size distributions obtained by DLS and TEM. A total of 205 particles are in the TEM image field (see). According to DLS, the obtained LNPs are dense particles with an average diameter of 73.6 ± 3.6 nm. The chemical shift anisotropy is ~22 (see Table 5), which is approximately two times smaller than the chemical shift anisotropy for liposomes from distaroylphosphatidylcholine. This means that the addition of Tyr-4686 to LNPs leads to the destruction of the lamellar phase and the formation of a more isotropic packing of lipid molecules. The shift of the peak of the phosphate group vibration band (Table 5) indicates the formation of hydrogen bonds between phospholipids.

[0102] [Table 5] Characteristics of Tyr-4686-based LNPs. Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Tyr-468673.6±3.6 nm22.5±3.0 ppm1220 cm -1

[0103] Example 6.

[0104] Asp-2610

[0105] [Structure of Asp-2610]

[0106] k = 1, l = 5, m = 9

[0107] Obtained according to example 1 from aspartic acid, decanol, chlorhexanoic acid and ethanolamine. 1H NMR (400 MHz): δ 0.87 (t, 12H, J = 7.00), 1.13-1.62 (m, 60H), 1.63-1.81 (m, 8H), 2.23 (t, 4H J = 7.37), 2.71 (t, 4H), 2.85 (2H, t, J = 2.67 Hz), 3.00 (d, 4H, J = 6.26 Hz), 3.54 (2H, t, J = 2.67 Hz), 4.15-4.29 (m, 8H)), 5.02 (2H, dd, J = 6.26, 6.26 Hz). 13C NMR (101 MHz): δ 14.00 (4C), 22.62 (4C), 25.41 (2C), 25.82 (4C), 27.11 (4C), 29.25 (4C), 29.36 (12C), 31.75 (4C), 36.41 (2C), 36.79 (2C), 49.50 (2C), 53.75 (2C), 57.00 (1C), 59.30 (1C), 65.17 (4C), 170.31 (2C), 171.89 (2C), 174.69 (2C). MS: M+ calculated 1079.8688; found 1079.8701.

[0108] Composition: Asp-2610, egg phosphatidylcholine (1:1 molar).

[0109] [Table 6] Characteristics of LNPs based on Asp-2610 Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Asp-2610108.6±18.5 nm21.2±2.1 ppm1227 cm -1

[0110] Example 7.

[0111] Asp-2612

[0112] [Structure of Asp-2612]

[0113] k = 1, l = 5, m = 11

[0114] Obtained according to example 1 from aspartic acid, dodecanol, chlorhexanoic acid and ethanolamine. 1H NMR (400 MHz): δ 0.85 (t, 12H, J = 7.00), 1.11-1.63 (m, 68H), 1.63-1.82 (m, 8H), 2.22 (t, 4H J = 7.37), 2.69 (t, 4H), 2.83 (2H, t, J = 2.67 Hz), 3.03 (d, 4H, J = 6.26 Hz), 3.56 (2H, t, J = 2.67 Hz), 4.13-4.29 (m, 8H)), 5.01 (2H, dd, J = 6.26, 6.26 Hz). 13C NMR (101 MHz): δ 14.00 (4C), 22.61 (4C), 25.39 (2C), 25.85 (4C), 27.15 (4C), 29.20 (4C), 29.37 (16C), 31.75 (4C), 36.39 (2C), 36.79 (2C), 49.53 (2C), 53.76 (2C), 57.01 (1C), 59.30 (1C), 65.17 (4C), 170.29 (2C), 171.89 (2C), 174.69 (2C). MS: M+ calculated 1191.9940; found 1191.9927.

[0115] Composition: Asp-2612, egg phosphatidylcholine (1:1 molar).

[0116] [Table 7] Characteristics of LNPs based on Asp-2612 Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Asp-2612123.2±25.6 nm20.8±2.5 ppm1230 cm -1

[0117] Example 8.

[0118] Asp-2614

[0119] [Structure of Asp-2614]

[0120] k = 1, l = 5, m = 13

[0121] Obtained according to example 1 from aspartic acid, tetradecanol, chlorhexanoic acid and ethanolamine. 1H NMR (400 MHz): δ 0.87 (t, 12H, J = 7.00), 1.12-1.60 (m, 76H), 1.63-1.82 (m, 8H), 2.27 (t, 4H J = 7.37), 2.73 (t, 4H), 2.80 (2H, t, J = 2.67 Hz), 3.02 (d, 4H, J = 6.26 Hz), 3.80 (2H, t, J = 2.67 Hz), 4.12-4.27 (m, 8H)), 5.00 (2H, dd, J = 6.26, 6.26 Hz). 13C NMR (101 MHz): δ 14.02 (4C), 22.64 (4C), 25.39 (2C), 25.83 (4C), 27.17 (4C), 29.18 (4C), 29.34 (20C), 31.73 (4C), 36.41 (2C), 36.79 (2C), 49.53 (2C), 53.73 (2C), 57.03 (1C), 59.31 (1C), 65.17 (4C), 170.25 (2C), 171.93 (2C), 174.67 (2C). MS: M+ calculated 1304.1192; found 1304.1188.

[0122] Composition: Asp-2614, egg phosphatidylcholine (1:1 molar)

[0123] [Table 8] Characteristics of LNPs based on Asp-2614 Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Asp-2614164.2±38.7 nm20.8±2.5 ppm1227 cm -1

[0124] Example 9.

[0125] Asp-2514

[0126] [Structure of Asp-2514]

[0127] k = 1, l = 4, m = 13

[0128] Obtained according to Example 1 from aspartic acid, tetradecanol, chloropentanoic acid, and ethanolamine. 1H NMR (400 MHz): δ 0.88 (t, 12H, J = 7.00), 1.13-1.60 (m, 76H), 1.63-1.81 (m, 8H), 2.72 (t, 4H), 2.81 (2H, t, J = 2.63 Hz), 3.01 (d, 4H, J = 6.24 Hz), 3.80 (2H, t, J = 2.67 Hz), 4.11-4.26 (m, 8H)), 5.02 (2H, dd, J = 6.26, 6.26 Hz). 13C NMR (101 MHz): δ 14.02 (4C), 22.64 (4C), 25.39 (2C), 25.83 (4C), 27.17 (4C), 29.18 (4C), 29.34 (20C), 31.73 (4C), 36.79 (2C), 49.53 (2C), 53.73 (2C), 57.03 (1C), 59.31 (1C), 65.17 (4C), 170.25 (2C), 171.93 (2C), 174.67 (2C). MS: M+ calculated 1276.0879; found 1276.0861.

[0129] Composition: Asp-2514, egg phosphatidylcholine (1:1 molar).

[0130] [Table 9] Characteristics of LNPs based on Asp-2514 Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Asp-2514158.2±35.3 nm23.2±1.8 ppm1225 cm-1

[0131] Example 10.

[0132] Asp-2513

[0133] [Structure of Asp-2513]

[0134] k = 1, l = 4, m = 12

[0135] Obtained according to Example 1 from aspartic acid, tridecanol, chloropentanoic acid and ethanolamine. 1H NMR (400 MHz): δ 0.87 (t, 12H, J = 7.00), 1.13-1.62 (m, 68H), 1.63-1.82 (m, 8H), 2.73 (t, 4H), 2.81 (2H, t, J = 2.62 Hz), 3.00 (d, 4H, J = 6.24 Hz), 3.80 (2H, t, J = 2.67 Hz), 4.11-4.26 (m, 8H)), 5.01 (2H, dd, J = 6.26, 6.26 Hz). 13C NMR (101 MHz): δ 14.02 (4C), 22.64 (4C), 25.39 (2C), 25.83 (4C), 27.17 (4C), 29.18 (4C), 29.33 (16C), 31.72 (4C), 36.78 (2C), 49.54 (2C), 53.72 (2C), 57.03 (1C), 59.32 (1C), 65.16 (4C), 170.25 (2C), 171.93 (2C), 174.67 (2C). MS: M+ calculated 1220.0253; found 1220.0259.

[0136] Composition: Asp-2513, egg phosphatidylcholine (1:1 molar).

[0137] [Table 10] Characteristics of LNPs based on Asp-2513 Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Asp-2513152.6±38.7 nm25.5±3.0 ppm1229 cm -1

[0138] Example 11.

[0139] Asp-4610

[0140] [Structure of Asp-4610]

[0141] k = 3, l = 5, m = 9

[0142] Obtained according to example 1 from aspartic acid, decanol, chlorhexanoic acid and butanolamine. 1H NMR (400 MHz): δ 0.87 (t, 12H, J = 7.00), 1.13-1.65 (m, 60H), 1.57-1.89 (m, 12H), 2.21 (t, 4H J = 7.37), 2.71 (t, 4H), 2.81 (2H, t, J = 2.67 Hz), 3.03 (d, 4H, J = 6.26 Hz), 3.53 (2H, t, J = 2.67 Hz), 4.13-4.27 (m, 8H)), 5.00 (2H, dd, J = 6.26, 6.25 Hz). 13C NMR (101 MHz): δ 14.00 (4C), 22.62 (4C), 25.41 (2C), 25.82 (4C), 27.2 (1C, s), 27.11 (4C), 29.25 (4C), 29.32 (12C), 31.75 (4C), 32.6 (1C, s) 36.40 (2C), 36.79 (2C), 49.50 (2C), 53.75 (2C), 57.00 (1C), 59.30 (1C), 65.17 (4C), 170.31 (2C), 171.89 (2C), 174.69 (2C). MS: M+ calculated 1107.9001; 1107,8988 found.

[0143] Composition: Asp-4610, egg phosphatidylcholine (1:1 molar).

[0144] [Table 11] Characteristics of Asp-4610-based LNPs Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Asp-4610110.3±19.8 nm23.6±2.8 ppm1229 cm -1

[0145] Example 12.

[0146] Asp-468

[0147] [Structure of Asp-468]

[0148] k = 3, l = 5, m = 7

[0149] Obtained according to example 1 from aspartic acid, octanol, chlorhexanoic acid and butanolamine. 1H NMR (400 MHz): δ 0.86 (t, 12H, J = 7.00), 1.13-1.63 (m, 52H), 1.60-1.88 (m, 12H), 2.21 (t, 4H J = 7.37), 2.70 (t, 4H), 2.80 (2H, t, J = 2.67 Hz), 3.03 (d, 4H, J = 6.25 Hz), 3.53 (2H, t, J = 2.63 Hz), 4.13-4.27 (m, 8H)), 5.00 (2H, dd, J = 6.24, 6.25 Hz). 13C NMR (101 MHz): δ 14.01 (4C), 22.65 (4C), 25.41 (2C), 25.81 (4C), 27.3 (1C, s), 27.11 (4C), 29.23 (4C), 29.31 (4C), 31.75 (4C), 32.6 (1C, s) 36.40 (2C), 36.79 (2C), 49.50 (2C), 53.73 (2C), 57.00 (1C), 59.30 (1C), 65.17 (4C), 170.30 (2C), 171.80 (2C), 174.69 (2C). MS: M+ calculated 995.7749; 995,7754 found.

[0150] Composition: Asp-468, egg phosphatidylcholine (1:1 molar).

[0151] [Table 12] Characteristics of Asp-468-based LNPs Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Asp-46898.2±13.2 nm21.8±2.7 ppm1225 cm -1

[0152] Example 13.

[0153] Asp-348

[0154] [Structure of Asp-348]

[0155] k = 2, l = 3, m = 7

[0156] Obtained according to example 1 from aspartic acid, octanol, chlorobutanoic acid and propanolamine. 1H NMR (400 MHz): δ 0.83 (t, 12H, J = 7.00), 1.15-1.67 (m, 52H), 1.67-1.85 (m, 8H), 2.21 (t, 4H J = 7.35), 2.73 (t, 2H), 2.85 (2H, t, J = 2.67 Hz), 2.99 (d, 4H, J = 6.26 Hz), 3.54 (2H, t, J = 2.67 Hz), 4.14-4.29 (m, 8H)), 5.01 (2H, dd, J = 6.25, 6.26 Hz). 13C NMR (101 MHz): δ 14.02 (4C), 22.63 (4C), 25.41 (2C), 25.87 (4C), 27.08 (4C), 29.23 (4C), 29.35 (8C), 32.00 (4C), 36.39 (1C), 36.81 (2C), 49.49 (2C), 53.72 (1C), 57.00 (1C), 59.31 (1C), 65.17 (4C), 170.31 (2C), 171.90 (2C), 174.70 (2C). MS: M+ calculated 925.6966; found 925.6947.

[0157] Composition: Asp-348, egg phosphatidylcholine (1:1 molar).

[0158] [Table 13] Characteristics of Asp-348-based LNPs Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Asp-348103.8±17.2 nm20.7±1.9 ppm1227 cm -1

[0159] Example 14.

[0160] Leu-3610

[0161] [Structure of Leu-3610]

[0162] k = 2, l = 5, m = 9

[0163] Obtained according to Example 2 from leucine, w-chlorohexanoic acid chloride, decanol, and propanolamine. 1H NMR (400 MHz): δ 0.80-0.97 (m, 18H), 1.13-1.86 (m, 52H)), 2.22 (t, 4H, J = 7.37 Hz), 2.70-2.82 (m, 4H), 3.35 (2H, t, J = 7.02 Hz), 4.12-4.37 (m, 6H)). 13C NMR (101 MHz): δ 14.00 (2C), 19.71 (1C), 22.62 (4C), 22.72 (2C), 24.33 (2C), 25.44 (2C), 25.83 (2C), 27.31 (2C), 27.20 (2C), 29.27 (2C), 29.43 (8C), 30.03 (1C), 32.06 (1C), 36.82 (2C), 40.96 (2C), 52.53 (2C), 53.71 (3C), 62.21 (1C), 65.17 (2C), 170.41 (2C), 174.63 (2C). MS: M+ calculated 809.6857; 809,6865 found.

[0164] Composition: Leu-3610, distearoylphosphatidylcholine (DSPC), cholesterol (1 / 1 / 0.2 mol.).

[0165] [Table 14] Characteristics of Leu-3610-based LNPs Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Leu-3610118.0±15.6 nm23.2±2.3 ppm1220 cm -1

[0166] Example 15.

[0167] Leu-3710

[0168] [Structure of Leu-3710]

[0169] k = 2, l = 6, m = 9

[0170] Obtained according to Example 2 from leucine, w-chloroheptanoic acid chloride, decanol, and propanolamine. 1H NMR (400 MHz): δ 0.81-0.97 (m, 18H), 1.12-1.87 (m, 52H)), 2.21 (t, 4H, J = 7.37 Hz), 2.69-2.89 (m, 8H), 3.35 (2H, t, J = 7.02 Hz), 4.12-4.37 (m, 6H)). 13C NMR (101 MHz): δ 14.00 (2C), 19.72 (1C), 22.61 (8C), 22.72 (2C), 24.33 (2C), 25.44 (2C), 25.83 (2C), 27.31 (2C), 27.20 (2C), 29.27 (2C), 29.43 (8C), 30.03 (1C), 32.06 (1C), 36.82 (2C), 40.96 (2C), 52.53 (2C), 53.71 (3C), 62.21 (1C), 65.18 (2C), 170.41 (2C), 174.63 (2C). MS: M+ calculated 837.7170; 837,7181 found.

[0171] Composition: Leu-3710, distearoylphosphatidylcholine (DSPC), cholesterol (1 / 1 / 0.2 mol.).

[0172] [Table 15] Characteristics of Leu-3710-based LNPs Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Leu-3710121.0±16.9 nm23.8±2.9 ppm1224 cm -1

[0173] Example 16.

[0174] Leu-379

[0175] [Structure of Leu-379]

[0176] k = 2, l = 6, m = 8

[0177] Obtained according to Example 2 from leucine, w-chloroheptanoic acid chloride, nonanol, and propanolamine. 1H NMR (400 MHz): δ 0.81-0.97 (m, 18H), 1.12-1.86 (m, 48H)), 2.22 (t, 4H, J = 7.36 Hz), 2.69-2.88 (m, 8H), 3.33 (2H, t, J = 7.02 Hz), 4.12-4.37 (m, 6H)). 13C NMR (101 MHz): δ 14.01 (2C), 19.73 (1C), 22.60 (6C), 22.72 (2C), 24.32 (2C), 25.47 (2C), 25.82 (2C), 27.31 (2C), 27.20 (2C), 29.27 (2C), 29.43 (8C), 30.03 (1C), 32.06 (1C), 36.82 (2C), 40.96 (2C), 52.53 (2C), 53.71 (3C), 62.21 (1C), 65.18 (2C), 170.41 (2C), 174.63 (2C). MS: M+ calculated 809.6857; 809,6863 found.

[0178] Composition: Leu-379, distearoylphosphatidylcholine (DSPC), cholesterol (1 / 1 / 0.2 mol.).

[0179] [Table 16] Characteristics of Leu-379-based LNPs Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Leu-379118.6±15.3 nm23.4±3.1 ppm1227 cm -1

[0180] Example 17.

[0181] Leu-3711

[0182] [Structure of Leu-3711]

[0183] k = 2, l = 6, m = 10

[0184] Obtained according to Example 2 from leucine, w-chloroheptanoic acid chloride, undecanol, and propanolamine. 1H NMR (400 MHz): δ 0.80-0.98 (m, 18H), 1.12-1.88 (m, 54H)), 2.23 (t, 4H, J = 7.37 Hz), 2.68-2.89 (m, 8H), 3.34 (2H, t, J = 7.02 Hz), 4.12-4.37 (m, 6H)). 13C NMR (101 MHz): δ 14.00 (2C), 19.72 (1C), 22.61 (10C), 22.72 (2C), 24.33 (2C), 25.44 (2C), 25.83 (2C), 27.31 (2C), 27.20 (2C), 29.27 (2C), 29.43 (8C), 30.03 (1C), 32.06 (1C), 36.82 (2C), 40.96 (2C), 52.53 (2C), 53.71 (3C), 62.21 (1C), 65.18 (2C), 170.41 (2C), 174.63 (2C). MS: M+ calculated 865.7483; 865,7489 found.

[0185] Composition: Leu-3711, distearoylphosphatidylcholine (DSPC), cholesterol (1 / 1 / 0.2 mol.).

[0186] [Table 17] Characteristics of Leu-3711-based LNPs Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Leu-3711127.0±17.3 nm23.0±2.5 ppm1226 cm -1

[0187] Example 18.

[0188] Leu-2610

[0189] [Structure of Leu-2610]

[0190] k = 1, l = 5, m = 9

[0191] Obtained according to Example 2 from leucine, w-chlorohexanoic acid chloride, decanol, and ethanolamine. 1H NMR (400 MHz): δ 0.80-0.97 (m, 18H), 1.12-1.86 (m, 52H)), 2.25 (t, 4H, J = 7.36 Hz), 2.71-2.81 (m, 4H), 3.34 (2H, t, J = 7.01 Hz), 4.12-4.36 (m, 6H)). 13C NMR (101 MHz): δ 14.00 (2C), 19.71 (1C), 22.62 (4C), 22.72 (2C), 24.33 (2C), 25.44 (2C), 25.83 (2C), 27.31 (2C), 27.20 (2C), 29.27 (2C), 29.43 (8C), 30.03 (1C), 32.06 (1C), 36.82 (2C), 40.96 (2C), 52.53 (2C), 53.71 (3C), 62.21 (1C), 65.17 (2C), 170.41 (2C), 174.63 (2C). MS: M+ calculated 795.6700; 795,6708 found.

[0192] Composition: Leu-2610, distearoylphosphatidylcholine (DSPC), cholesterol (1 / 1 / 0.2 mol.).

[0193] [Table 18] Characteristics of Leu-2610-based LNPs Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Leu-2610101.0±12.1 nm25.7±2.8 ppm1226 cm -1

[0194] Example 19.

[0195] Leu-268

[0196] [Structure of Leu-268]

[0197] k = 1, l = 5, m = 9

[0198] Obtained according to Example 2 from leucine, w-chlorohexanoic acid chloride, octanol, and ethanolamine. 1H NMR (400 MHz): δ 0.81-0.95 (m, 18H), 1.13-1.83 (m, 46H)), 2.23 (t, 4H, J = 7.33 Hz), 2.70-2.87 (m, 6H), 3.35 (2H, t, J = 7.00 Hz), 4.13-4.35 (m, 6H)). 13C NMR (101 MHz): δ 14.01 (2C), 19.79 (1C), 22.57 (4C), 22.63 (2C), 24.38 (2C), 25.40 (2C), 25.85 (2C), 27.14 (2C), 27.23 (2C), 29.29 (2C), 29.42 (2C), 30.10 (1C), 31.85 (2C), 36.80 (2C), 40.93 (2C), 52.62 (2C), 53.69 (3C), 62.23 (1C), 65.18 (2C), 170.31 (2C), 174.68 (2C). MS: M+ calculated 823.7013; 823,6997 found.

[0199] Composition: Leu-268, distearoylphosphatidylcholine (DSPC), cholesterol (1 / 1 / 0.2 mol.).

[0200] [Table 19] Characteristics of Leu-268-based LNPs Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Leu-26894.0±10.6 nm25.2±2.5 ppm1224 cm -1

[0201] Example 20.

[0202] Ile-4612

[0203] [Structure of Ile-4612]

[0204] k = 3, l = 5, m = 11

[0205] Obtained according to scheme P2 from isoleucine, w-chlorohexanoic acid chloride, dodecanol, and butanolamine. 1H NMR (400 MHz): δ 0.77-0.95 (m 18H), 1.14-1.99 (m 62H), 2.15-2.28 (m, 4H), 2.70-2.82 (m 6H), 3.34 (2H, t, J = 7.02 Hz), 4.11-4.27 (6H). 13C NMR (101 MHz): δ 10.95 (2C, s), 14.05 (2C, s), 15.18 (2C, s), 22.65 (2C, s), 24.67 (2C, s), 25.70 (2C, s), 25.90 (2C, s), 26.10 (2C, s), 27.21 (1C, s), 27.62 (2C, s), 28.54 (2C, s), 29.30-29.45 (4C), 29.59-29.71 (8C), 31.91 (2C, s), 32.60 (1C, s), 36.80 (2C, s), 37.10 (2C, s), 54.45-54.55 (3C), 57.10 (2C, s), 62.56 (1C, s), 64.47 (2C, s), 171.62 (2C, s), 172.00 (2C, s).

[0206] Composition: Ile-4612, distearoylphosphatidylcholine (DSPC), cholesterol (1 / 1 / 0.2 mol.).

[0207] [Table 20] Characteristics of LNPs based on Ile-4612 Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Ile-4612123.0±19.1 nm24.1±2.7 ppm1226 cm -1

[0208] Example 21.

[0209] Ile-4614

[0210] [Structure of Ile-4614]

[0211] k = 3, l = 5, m = 13

[0212] Obtained according to Example 2 from isoleucine, w-chlorohexanoic acid chloride, tetradecanol, and butanolamine. 1H NMR (400 MHz): δ 0.76-0.94 (m 18H), 1.14-1.98 (m 70H), 2.15-2.28 (m, 4H), 2.72-2.82 (m 6H), 3.33 (2H, t, J = 7.02 Hz), 4.11-4.28 (6H). 13C NMR (101 MHz): δ 10.96 (2C, s), 14.04 (2C, s), 15.19 (2C, s), 22.65 (2C, s), 24.67 (2C, s), 25.70 (4C, s), 25.90 (4C, s), 26.10 (2C, s), 27.23 (1C, s), 27.62 (2C, s), 28.54 (2C, s), 29.30-29.45 (4C), 29.59-29.71 (8C), 31.93 (2C, s), 32.23 (1C, s), 36.81 (2C, s), 37.12 (2C, s), 54.42-54.57 (3C), 57.13 (2C, s), 62.53 (1C, s), 64.87 (2C, s), 171.61 (2C, s), 172.02 (2C, s).

[0213] Composition: Ile-4614, distearoylphosphatidylcholine (DSPC), cholesterol (1 / 1 / 0.2 mol.).

[0214] [Table 21] Characteristics of LNPs based on Ile-4614 Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Ile-4614173.0±34.7 nm29.1±5.6 ppm1235 cm -1

[0215] Example 22.

[0216] Ile-2610

[0217] [Structure of Ile-2610]

[0218] k = 1, l = 5, m = 9

[0219] Obtained according to Example 2 from isoleucine, w-chlorohexanoic acid chloride, decanol, and ethanolamine. 1H NMR (400 MHz): δ 0.77-0.95 (m, 18H), 1.14-1.62 (m, 44H), 1.65-1.99 (m, 6H), 2.15-2.28 (m, 4H), 2.66-2.77 (m, 4H), 2.85 (2H, t, J = 2.67 Hz), 3.54 (2H, t, J = 2.67 Hz), 4.11-4.27 (m, 6H). 13C NMR (101 MHz): δ 10.95 (2C, s), 14.05 (2C, s), 15.18 (2C, s), 22.65 (2C, s), 24.67 (2C, s), 25.70 (2C, s), 25.90 (2C, s), 26.10 (2C, s), 27.62 (2C, s), 28.54 (2C, s), 29.30-29.45 (4C), 29.59-29.71 (4C), 31.91 (2C, s), 36.80 (2C, s), 37.10 (2C, s), 54.50 (2C, s), 56.79 (1C, s), 57.10 (2C, s), 59.97 (1C, s), 64.47 (2C, s), 171.62 (2C, s), 172.00 (2C, s). MS: M+ calculated 795.6700; found 795.6689.

[0220] Composition: Ile-2610, distearoylphosphatidylcholine (DSPC), cholesterol (1 / 1 / 0.2 mol.).

[0221] [Table 22] Characteristics of LNPs based on Ile-2610 Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Ile-261093.0±14.2 nm23.1±3.2 ppm1220 cm -1

[0222] Example 23.

[0223] Ile-2410

[0224] [Structure of Ile-2410]

[0225] k = 1, l = 3, m = 9

[0226] Obtained according to Example 2 from isoleucine, w-chlorobutanoic acid chloride, decanol, and ethanolamine. 1H NMR (400 MHz): δ 0.77-0.97 (m, 18H), 1.14-1.47 (m 32H), 1.65-1.99 (m10H), 2.21-2.34 (m 4H), 2.66-2.78 (m 4H), 2.86 (2H, t, J = 2.67 Hz), 3.55 (2H, t, J = 2.67 Hz), 4.11-4.27 (m 6H). 13C NMR (101 MHz): δ 10.95 (2C, s), 14.05 (2C, s), 15.18 (2C, s), 22.65 (2C, s), 24.40 (2C, s), 24.67 (2C, s), 25.90 (2C, s), 28.54 (2C, s), 29.30-29.45 (4C), 29.59-29.71 (4C), 31.91 (2C, s), 34.40 (2C, s), 37.10 (2C, s), 53.97 (2C, s), 56.79 (1C, s), 57.10 (2C, s), 59.97 (1C, s), 64.47 (2C, s), 171.62 (2C, s), 172.00 (2C, s). MS: M+ calculated 739.6074; found: 739.6071.

[0227] Composition: Ile-2410, distearoylphosphatidylcholine (DSPC), cholesterol (1 / 1 / 0.2 mol.).

[0228] [Table 23] Characteristics of LNPs based on Ile-2410 Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Ile-241097.0±13.6 nm23.7±3.4 ppm1223 cm -1

[0229] Example 24.

[0230] Ile-288

[0231] [Structure of Ile-288]

[0232] k = 1, l = 7, m = 7

[0233] Obtained according to scheme P2 from isoleucine, w-chlorooctanoic acid chloride, octanol, and ethanolamine. 1H NMR (400 MHz): δ 0.77-0.95 (m 18H), 1.14-1.62 (m 44H), 1.65-1.99 (m 6H), 2.15-2.28 (m 4H), 2.66-2.77 (m 4H), 2.85 (2H, t, J = 2.67 Hz), 3.54 (2H, t, J = 2.67 Hz), 4.11-4.27 (m 6H). 13C NMR (101 MHz): δ 10.95 (2C, s), 14.05 (2C, s), 15.18 (2C, s), 22.65 (2C, s), 24.67 (2C, s), 25.70 (2C, s), 25.90 (2C, s), 27.10 (2C, s), 27.73 (2C, s), 28.54 (2C, s), 29.25-29.45 (6C), 29.60 (2C, s), 31.91 (2C, s), 36.80 (2C, s), 37.10 (2C, s), 54.50 (2C, s), 56.79 (1C, s), 57.10 (2C, s), 59.97 (1C, s), 64.47 (2C, s), 171.62 (2C, s), 172.00 (2C, s). MS: M+ calculated 795.6700; found: 795.6713.

[0234] Composition: Ile-288, distearoylphosphatidylcholine (DSPC), cholesterol (1 / 1 / 0.2 mol.).

[0235] [Table 24] Characteristics of LNPs based on Ile-288 Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Ile-288888.0±11.4 nm20.1±2.7 ppm1229 cm -1

[0236] Example 25.

[0237] Val-4610

[0238] [Structure Val-4610]

[0239] k = 3, l = 5, m = 9

[0240] Obtained according to Example 2 from valine, w-chlorhexyl chloride, decanol, and butanolamine. 1H NMR (400 MHz): δ 0.80-0.93 (m 18H), 1.14-1.86 (48H), 1.94-2.28 (m 6H), 2.71-2.83 (m 6H), 3.34 (2H, t, J = 7.02 Hz), 4.07-4.27 (m 6H). 13C NMR (101 MHz): δ 14.05 (2C, s), 18.40 (2C, s), 18.98 (2C, s), 22.65 (2C, s), 25.70 (2C, s), 25.90 (2C, s), 26.10 (2C, s), 27.21 (1C, s), 27.62 (2C, s), 28.54 (2C, s), 29.30-29.45 (4C), 29.59-29.71 (4C), 31.08 (2C, s), 31.91 (2C, s), 32.60 (1C, s), 36.80 (2C, s), 54.45-54.55 (3C), 57.47 (2C, s), 62.56 (1C, s), 64.47 (2C, s), 171.61 (2C, s), 172.01 (2C, s). MS: M+ calculated 795.6700; found: 795.6711.

[0241] Composition: Val-4610, distearoylphosphatidylcholine (DSPC), cholesterol (1 / 1 / 0.2 mol.).

[0242] [Table 25] Characteristics of Val-4610-based LNPs Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Val-4610110.3±19.4 nm23.6±2.4 ppm1227 cm -1

[0243] Example 26.

[0244] Val-468

[0245] [Structure of Val-468]

[0246] k = 3, l = 5, m = 7

[0247] Obtained according to Example 2 from valine, w-chlorhexyl chloride, octanol, and butanolamine. 1H NMR (400 MHz): δ 0.80-0.93 (m 18H), 1.14-1.86 (m 48H), 1.94-2.28 (m 6H), 2.71-2.83 (m 6H), 3.34 (2H, t, J = 7.02 Hz), 4.07-4.27 (m 6H). 13C NMR (101 MHz): δ 14.03 (2C, s), 18.42 (2C, s), 18.97 (2C, s), 22.63 (2C, s), 25.70 (2C, s), 25.91 (2C, s), 26.11 (2C, s), 27.21 (1C, s), 27.63 (2C, s), 28.53 (2C, s), 29.25-29.45 (4C, 29.30 (s), 29.40 (s)), 31.08 (2C, s), 31.91 (2C, s), 32.60 (1C, s), 36.80 (2C, s), 54.45-54.55 (3C), 57.47 (2C, s), 62.56 (1C, s), 64.47 (2C, s), 171.61 (2C, s), 172.02 (2C, s). MS: M+ calculated 739.6074; found: 739.6067.

[0248] Composition: Val-468, distearoylphosphatidylcholine (DSPC), cholesterol (1 / 1 / 0.2 mol.).

[0249] [Table 26] Characteristics of Val-468-based LNPs Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Val-468102.1±10.9 nm27.1±2.7 ppm1229 cm -1

[0250] Example 27.

[0251] Glu-488

[0252] [Structure of Glu-488]

[0253] k = 3, l = 7, m = 7

[0254] Obtained according to Example 3 from glutamic acid, w-chlorhexidine acid, octanol, and butanolamine. 1H NMR (400 MHz): δ 0.87 (t, 12H, J = 7.00)), 1.14-2.01 (m, 68H), 2.22 (4H, t, J = 7.37 Hz), 2.40 (t, 4H, 2.40, J = 7.37 Hz), 2.71-2.83 (m, 6H)), 3.34 (2H, t, J = 7.02 Hz), 4.14-4.43 (m, 10H). 13C NMR (101 MHz): δ 14.02 (4C), 19.79 (1C), 22.63 (4C), 25.40 (2C), 25.82 (4C), 26.19 (2C), 27.10 (4C), 29.26 (4C), 29.40 (8C), 30.00 (1C), 31.14 (2C), 31.75 (4C), 36.80 (2C), 52.60 (2C), 53.74 (3C), 62.20 (1C), 65.17 (4C), 170.30 (2C), 173.00 (2C), 174.70 (2C). MS: M+ calculated 1023.8062; 1023,8011 found.

[0255] Composition: Glu-488, distearoylphosphatidylcholine (DSPC), (1 / 1 mol.).

[0256] [Table 27] Characteristics of Glu-488-based LNPs Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Glu-48884.1±13.0 nm17.9±3.2 ppm1223 cm -1

[0257] Example 28.

[0258] Glu-4810

[0259] [Structure of Glu-4810]

[0260] k = 3, l = 7, m = 9

[0261] Obtained according to Example 3 from glutamic acid, w-chlorhexidine acid, octanol, and butanolamine. 1H NMR (400 MHz): δ 0.87 (t, 12H, J = 7.00)), 1.14-2.01 (m, 68H), 2.22 (4H, t, J = 7.37 Hz), 2.40 (t, 4H, 2.40, J = 7.37 Hz), 2.71-2.83 (m, 6H)), 3.34 (2H, t, J = 7.02 Hz), 4.14-4.43 (m, 10H). 13C NMR (101 MHz): δ 14.02 (4C), 19.79 (1C), 22.63 (4C), 25.40 (2C), 25.82 (4C), 26.19 (2C), 27.10 (4C), 29.26 (4C), 29.40 (8C), 30.00 (1C), 31.14 (2C), 31.75 (4C), 36.80 (2C), 52.60 (2C), 53.74 (3C), 62.20 (1C), 65.17 (4C), 170.30 (2C), 173.00 (2C), 174.70 (2C). MS: M+ calculated 1023.8062; 1023,8011 found.

[0262] Composition: Glu-4810, distearoylphosphatidylcholine (DSPC), (1 / 1 mol.).

[0263] [Table 28] Characteristics of Glu-4810-based LNPs Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Glu-481097.9±18.5 nm21.7±3.9 ppm1227 cm-1

[0264] Example 29.

[0265] Glu-4812

[0266] [Structure of Glu-4812]

[0267] k = 3, l = 7, m = 11

[0268] Obtained according to Example 3 from glutamic acid, w-chlorooctanoic acid, dodecanol, and butanolamine. 1H NMR (400 MHz): δ 0.87 (t, 12H, J = 7.01)), 1.14-2.12 (m, 100H), 2.24 (4H, t, J = 7.37 Hz), 2.41 (t, 4H, 2.40, J = 7.37 Hz), 2.70-2.83 (m, 6H)), 3.33 (2H, t, J = 7.02 Hz), 4.14-4.43 (m, 10H). 13C NMR (101 MHz): δ 14.02 (4C), 19.79 (1C), 22.61 (12C), 25.40 (2C), 25.80 (4C), 26.21 (2C), 27.12 (4C), 29.25 (8C), 29.40 (8C), 30.00 (1C), 31.13 (2C), 31.73 (4C), 36.82 (2C), 52.59 (2C), 53.76 (3C), 62.20 (1C), 65.19 (4C), 170.30 (2C), 173.00 (2C), 174.70 (2C). MS: M+ calculated 1304.1921; found 1304,1929.

[0269] Composition Glu-4812, distearoylphosphatidylcholine (DSPC), (1 / 1 mol.).

[0270] [Table 29] Characteristics of Glu-4812-based LNPs Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Glu-4812121±23.3 nm27.1±2.6 ppm1225 cm -1

[0271] Example 30.

[0272] Glu-268

[0273] [Structure of Glu-268]

[0274] k = 1, l = 5, m = 7

[0275] Obtained according to Example 3 from glutamic acid, w-chlorhexidine acid, octanol, and ethanolamine. 1H NMR (400 MHz): δ 0.87 (t, 12H, J = 7.00)), 1.13-2.00 (m, 68H), 2.26 (4H, t, J = 7.35 Hz), 2.41 (t, 4H, 2.40, J = 7.37 Hz), 2.70-2.81 (m, 2H), 3.34 (2H, t, J = 7.02 Hz), 4.14-4.43 (m, 10H). 13C NMR (101 MHz): δ 14.02 (4C), 19.79 (1C), 22.63 (4C), 25.40 (2C), 25.82 (4C), 26.19 (2C), 27.10 (4C), 29.26 (4C), 29.40 (8C), 30.00 (1C), 31.14 (2C), 31.71 (4C), 36.80 (2C), 52.61 (1C), 53.73 (2C), 62.20 (1C), 65.17 (4C), 170.30 (2C), 173.00 (2C), 174.70 (2C). MS: M+ calculated 1023.8062; 1023,8011 found.

[0276] Composition: Glu-268, distearoylphosphatidylcholine (DSPC), (1 / 1 mol.).

[0277] [Table 30] Characteristics of Glu-268-based LNPs Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Glu-26850.2±7.1 nm14.7±1.5 ppm1217 cm-1

[0278] Example 31.

[0279] Glu-269

[0280] [Structure of Glu-269]

[0281] k = 1, l = 5, m = 8

[0282] Obtained according to Example 3 from glutamic acid, w-chlorhexidine acid, nonanol, and ethanolamine. 1H NMR (400 MHz): δ 0.86 (t, 12H, J = 7.00)), 1.11-2.00 (m, 76H), 2.26 (4H, t, J = 7.35 Hz), 2.41 (t, 4H, 2.40, J = 7.37 Hz), 2.70-2.81 (m, 2H), 3.34 (2H, t, J = 7.02 Hz), 4.14-4.43 (m, 10H). 13C NMR (101 MHz): δ 14.02 (4C), 19.79 (1C), 22.64 (4C), 25.41 (2C), 25.80 (4C), 26.21 (2C), 27.10 (4C), 29.26 (4C), 29.41 (12C), 30.00 (1C), 31.14 (2C), 31.71 (4C), 36.80 (2C), 52.61 (1C), 53.72 (2C), 62.22 (1C), 65.17 (4C), 170.30 (2C), 173.00 (2C), 174.70 (2C). MS: M+ calculated 1079.8688; 1079,8692 found.

[0283] Composition: Glu-269, distearoylphosphatidylcholine (DSPC), (1 / 1 mol.).

[0284] [Table 31] Characteristics of Glu-269-based LNPs Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Glu-26958.8±5.6 nm16.2±1.7 ppm1219 cm -1

[0285] Example 32.

[0286] Glu-267

[0287] [Structure of Glu-267]

[0288] k = 1, l = 5, m = 6

[0289] Obtained according to Example 3 from glutamic acid, w-chlorhexidine acid, heptanol, and ethanolamine. 1H NMR (400 MHz): δ 0.86 (t, 12H, J = 7.00)), 1.13-2.05 (m, 60H), 2.22 (4H, t, J = 7.35 Hz), 2.40 (t, 4H, 2.40, J = 7.37 Hz), 2.72-2.81 (m, 2H), 3.34 (2H, t, J = 7.02 Hz), 4.14-4.43 (m, 10H). 13C NMR (101 MHz): δ 14.01 (4C), 19.79 (1C), 22.63 (4C), 25.41 (2C), 25.82 (4C), 26.19 (2C), 27.10 (4C), 29.26 (4C), 29.41 (4C), 30.00 (1C), 31.14 (2C), 31.71 (4C), 36.80 (2C), 52.61 (1C), 53.73 (2C), 62.20 (1C), 65.17 (4C), 170.30 (2C), 173.02 (2C), 174.71 (2C). MS: M+ calculated 939.7123; 939,7134 found.

[0290] Composition: Glu-267, distearoylphosphatidylcholine (DSPC), (1 / 1 mol.).

[0291] [Table 32] Characteristics of Glu-267-based LNPs Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Glu-26747.5±6.5 nm13.6±1.6 ppm1215 cm-1

[0292] Example 33.

[0293] Glu-266

[0294] [Structure of Glu-266]

[0295] k = 1, l = 5, m = 5

[0296] Obtained according to Example 3 from glutamic acid, w-chlorhexidine acid, hexanol, and ethanolamine. 1H NMR (400 MHz): δ 0.88 (t, 12H, J = 7.00)), 1.13-2.05 (m, 54H), 2.23 (4H, t, J = 7.35 Hz), 2.41 (t, 4H, 2.40, J = 7.36 Hz), 2.72-2.80 (m, 2H), 3.34 (2H, t, J = 7.02 Hz), 4.14-4.43 (m, 10H). 13C NMR (101 MHz): δ 14.00 (4C), 19.79 (1C), 22.63 (4C), 25.41 (2C), 25.82 (4C), 26.19 (2C), 27.10 (4C), 29.26 (4C), 29.40 (2C), 30.00 (1C), 31.14 (2C), 31.71 (4C), 36.80 (2C), 52.61 (1C), 53.73 (2C), 62.20 (1C), 65.17 (4C), 170.30 (2C), 173.02 (2C), 174.71 (2C). MS: M+ calculated 883.6497; 883,6489 found.

[0297] Composition: Glu-266, distearoylphosphatidylcholine (DSPC), (1 / 1 mol.).

[0298] [Table 33] Characteristics of Glu-266-based LNPs Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Glu-26642.3±5.2 nm13.4±1.8 ppm1217 cm -1

[0299] Example 34.

[0300] Glu-265

[0301] [Structure of Glu-265]

[0302] k = 1, l = 5, m = 4

[0303] Obtained according to Example 3 from glutamic acid, w-chlorhexidine acid, pentanol, and ethanolamine. 1H NMR (400 MHz): δ 0.88 (t, 12H, J = 7.00)), 1.13-2.05 (m, 46H), 2.23 (4H, t, J = 7.35 Hz), 2.41 (t, 4H, 2.40, J = 7.36 Hz), 2.72-2.80 (m, 2H), 3.34 (2H, t, J = 7.02 Hz), 4.14-4.43 (m, 10H). 13C NMR (101 MHz): δ 14.00 (4C), 19.79 (1C), 22.63 (4C), 25.41 (2C), 25.82 (4C), 26.19 (2C), 27.10 (4C), 29.26 (4C), 30.00 (1C), 31.14 (2C), 31.71 (4C), 36.80 (2C), 52.61 (1C), 53.73 (2C), 62.20 (1C), 65.17 (4C), 170.30 (2C), 173.02 (2C), 174.71 (2C). MS: M+ calculated 827.5871; found 827.5868.

[0304] Composition: Glu-265, distearoylphosphatidylcholine (DSPC), (1 / 1 mol.).

[0305] [Table 34] Characteristics of Glu-265-based LNPs Sample Diameter (DLS), nm Chemical shift anisotropy 31 P NMR. ,ppmPosition of the maximum of component A, vibrations of the phosphatine group in the IR spectrum of LNP based on Glu-26539.5±5.8 nm13.8±2.3 ppm1219 cm -1

Claims

1. A surfactant containing branched hydrophobic chains with amino acid residues at the branching point is characterized by the general formula Where k can be equal to 1, 2 or 3;l can be equal to 3, 4, 5, 6 or 7;amino acid residue in L-configuration; R1 and R2 are the same or different residues from the following list: m is an integer from 4 to 13.

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