Polyalkylene glycol lipid having alkyne group

Abstract

This polyalkylene glycol lipid is represented by formula (1). (R1 and R2 are each independently a hydrogen atom, an aliphatic hydrocarbon group having 15-22 carbon atoms, or an acyl group having 15-22 carbon atoms; 6≥k≥0, 6≥l≥0, 6≥m≥0 and k+l+m≥2; A is an oxygen atom, an ester bond, a carbonate bond, or a carbamate bond; B is a divalent hydrocarbon group having 1-4 carbon atoms; n is a number from 21 to 226; C is a divalent hydrocarbon group having 1-4 carbon atoms; D is an oxygen atom, an ester bond, a carbonate bond, a carbamate bond, a urea bond, or an amide bond; E is a single bond or a divalent hydrocarbon group having 1-6 carbon atoms; and G is an atomic group represented by formula (2a), formula (2b), formula (2c), formula (2d), formula (2e), or formula (2f) described in the description.)

Description

Polyalkylene glycol lipids having alkyne groups

[0001] This invention relates to polyalkylene glycol lipids having alkyne groups.

[0002] In the field of drug delivery systems, research on lipid nanoparticles (LNPs) containing nucleic acids is widespread. These LNPs are microparticles composed of phospholipids, cholesterol, polyethylene glycol (PEG) lipids, and ionized lipids. Because their surface is covered with PEG, they help protect nucleic acids from enzymatic degradation. As a result, LNPs exhibit high blood retention and interact with and accumulate in various cells in the liver (hepatocytes, endothelial cells, B cells, and Kupffer cells), making them useful for nucleic acid delivery targeting hepatocytes.

[0003] To immobilize PEG lipids on the LNP surface, long-chain aliphatic hydrocarbon groups or acyl groups are introduced into the PEG lipids. However, if the number of carbon atoms in the aliphatic hydrocarbon group or acyl group is short, the PEG lipids are not sufficiently immobilized on the LNP surface, and as a result, the PEG lipids are rapidly released into the bloodstream, leading to low blood retention of LNPs and accumulation in the liver, as has been reported (Non-Patent Literature 1).

[0004] Since the PEG on the surface of LNPs is derived from PEG lipids, which are components of LNPs, if a reactive group that can bind ligands can be introduced to the PEG terminus of the PEG lipid, ligands can be immobilized on the LNP surface, thereby conferring targeting ability to target organs. For this reason, selecting an appropriate reactive group that reacts with the ligand is important. Examples of reactive sites in antibodies include the thiol group of the cysteine ​​side chain and the amino group of the lysine side chain, and since the thiol group is known to react readily with the maleimide group, maleimide PEG lipids have been reported (Patent Document 1).

[0005] Furthermore, a click reaction between an azide group and an alkyne group is known as a highly specific coupling method, and coupling between alkyne PEG phospholipids and proteins has been reported (Non-Patent Literature 2).

[0006] International Publication No. 2022 / 065263

[0007] Mol Ther Nucleic Acids. 2013 ;2(12):e139. J Biosci Bioeng. 2017; 124 (4): 445-451.

[0008] However, although there are examples of delivery to the liver using LNPs, in order to deliver nucleic acids to more diverse organs, it is necessary to introduce a ligand that recognizes cell surface receptors, such as antibodies, aptamers, peptides, and sugar chains, to the PEG terminus on the surface of the LNP to improve targeting ability to the target organ. However, LNP base materials capable of delivering nucleic acids to diverse organs have not been obtained.

[0009] The PEG lipid described in Non-Patent Document 1 is not preferable as a PEG lipid for imparting organ tropism of LNPs to organs other than the liver. Furthermore, in the case of the maleimide PEG lipid described in Patent Document 1, since the aforementioned amino acid residues are widely present in antibodies, it is difficult to control the introduced amount. Furthermore, the PEG phospholipid described in Non-Patent Document 2 is not preferable particularly as a base material for LNPs encapsulating nucleic acids, since the phosphate group site has an electric charge.

[0010] As described above, further improvement has been required for PEG lipids as base materials for LNPs having organ tropism to organs other than the liver.

[0011] An object of the present invention is to provide a novel PEG lipid that has both sufficient immobilization ability on the LNP surface and a highly specific functional group.

[0012] The inventors of the present invention have conducted intensive studies to solve the above problems, and as a result, have found a PEG lipid having no phosphate group, a lipid moiety into which a hydrocarbon group having 15 to 22 carbon atoms or an acyl group is introduced, and an alkyne at the terminal of the PEG chain, and completed the present invention.

[0013] That is, the present invention is as follows. [1] A polyalkylene glycol lipid represented by the following formula (1). (In formula (1), R １ and R ２each independently represent a hydrogen atom, an aliphatic hydrocarbon group having 15 to 22 carbon atoms or an acyl group having 15 to 22 carbon atoms, k, l and m are each independently a number satisfying 6≧k≧0, 6≧l≧0, 6≧m≧0 and k+l+m≧2, A represents an oxygen atom, an ester bond, a carbonate bond or a carbamate bond, B represents a divalent hydrocarbon group having 1 to 4 carbon atoms, n is a number from 21 to 226, C represents a divalent hydrocarbon group having 1 to 4 carbon atoms, D represents an oxygen atom, an ester bond, a carbonate bond, a carbamate bond, a urea bond or an amide bond, E represents a single bond or a divalent hydrocarbon group having 1 to 6 carbon atoms, and G represents an atomic group represented by the following formula (2a), formula (2b), formula (2c), formula (2d), formula (2e) or formula (2f).) (In formula (2a), formula (2b), formula (2c), formula (2d), formula (2e), and formula (2f), the wavy line indicates the binding site. In formula (2b), F represents a fluorine atom. In formula (2f), Ts represents a tosyl group.)

[0014] [2] The polyalkylene glycol lipid according to [1], wherein in formula (1), R １ and R ２ are each independently a linear and saturated acyl group having 15 to 20 carbon atoms.

[0015] [3] The polyalkylene glycol lipid according to [1] or [2], wherein in formula (1), k and m are 1, and l is 0.

[0016] [4] The polyalkylene glycol lipid according to any one of [1] to [3], wherein in formula (1), A is an oxygen atom.

[0017] [5] The polyalkylene glycol lipid according to any one of [1] to [4], wherein in formula (1), B is a divalent hydrocarbon group having 2 carbon atoms.

[0018] [6] The polyalkylene glycol lipid according to any one of [1] to [5], wherein in formula (1), C is a divalent hydrocarbon group having 2 carbon atoms.

[0019] [7] A polyalkylene glycol lipid according to any of [1] to [6], characterized in that D is a carbamate bond in formula (1).

[0020] [8] A polyalkylene glycol lipid according to any of [1] to [7], characterized in that, in formula (1), E is a divalent hydrocarbon group having 2 carbon atoms.

[0021] [9] A polyalkylene glycol lipid according to any of [1] to [8], characterized in that in formula (1), G is the atomic group represented by formula (2e).

[0022]

[10] A substrate for lipid nanoparticles, characterized by comprising any of the polyalkylene glycol lipids from [1] to [9].

[0023] The polyalkylene glycol lipid having an alkyne group according to the present invention possesses both sufficient immobilization ability on the LNP surface and highly specific functional groups, making it useful as a base for LNPs with diverse organ-specific properties other than liver.

[0024] Embodiments of the present invention will be described in detail below. The polyalkylene glycol lipid having an alkyne group of the present invention is represented by the following general formula (1).

[0025] In equation (1), R １ and R ２ Each of these is independently a hydrogen atom, an aliphatic hydrocarbon group having 15 to 22 carbon atoms, or an acyl group having 15 to 22 carbon atoms. This aliphatic hydrocarbon group may be linear or branched, saturated or unsaturated. This acyl group may also be linear or branched, saturated or unsaturated. Among these, a linear or branched, saturated or unsaturated aliphatic hydrocarbon group having 16 to 20 carbon atoms or a linear or branched, saturated or unsaturated acyl group having 16 to 20 carbon atoms is preferred. Furthermore, a linear and saturated acyl group having 16, 18, or 20 carbon atoms is particularly preferred.

[0026] These aliphatic hydrocarbon groups and acyl groups specifically include: pentadecyl group, hexadecyl group, heptadecyl group, octadecyl group, nonadecyl group, eicosyl group, pentadecenyl group, hexadecenyl group, heptadecenyl group, octadecenyl group, nonadecenyl group, eicocenyl group, pentadecadienyl group, hexadecadienyl group, heptadecienyl group, octadecadienyl group, nonadecienyl group, eicosadienyl group, octadecadrienyl group, eicosatrienyl group, eicosatetraenyl group, isostearyl group, pentadecanoyl group, hexadecanoyl group, heptadecanoyl group, octadecanoyl group, nonadecanoyl The following groups are preferred: arachidinoyl group, tetradecenylcarbonyl group, pentadecenylcarbonyl group, hexadecenylcarbonyl group, heptadecenylcarbonyl group, nonadecenylcarbonyl group, tetradecadienylcarbonyl group, pentadedecadienylcarbonyl group, hexadedecadienylcarbonyl group, heptadedecadienylcarbonyl group, octadedecadienylcarbonyl group, nonadedecadienylcarbonyl group, heptadedecatrienylonylcarbonyl group, nonadedecatrienylonylcarbonyl group, nonadedecatetraenylcarbonyl group, and isostearylcarbonyl group; hexadedecanoyl group, octadedecanoyl group, and arachidinoyl group are particularly preferred.

[0027] In equation (1), k, l, and m are numbers that independently satisfy 6≧k≧0, 6≧l≧0, 6≧m≧0, and k+l+m≧2. Here, 3≧k≧0, 3≧l≧0, and 3≧m≧0 are preferred, and the combination k=1, l=0, and m=1 is particularly preferred.

[0028] In formula (1), A is a stable binding mode that does not easily cleave during LNP preparation or in blood. Specifically, A is an oxygen atom, an ester bond, a carbonate bond, or a carbamate bond. An ester bond is "-O-C(O)-", a carbonate bond is "-O-C(O)-O-", and a carbamate bond is "-O-C(O)-N-". It is preferable that A is an oxygen atom, a carbonate bond, or a carbamate bond, with an oxygen atom being particularly preferred.

[0029] In formula (1), B is a divalent hydrocarbon group having 1 to 4 carbon atoms. The hydrocarbon group may be a straight-chain or branched, saturated or unsaturated hydrocarbon group, and is more preferably an alkylene group. Among these, a divalent hydrocarbon group having 2 carbon atoms is particularly preferred.

[0030] In formula (1), n ​​is the number of repeating units of alkylene glycol, specifically a number between 21 and 226. n is preferably 27 or greater, and more preferably 33 or greater. Furthermore, n is preferably 182 or less, and more preferably 135 or less.

[0031] In formula (1), C is a divalent hydrocarbon group having 1 to 4 carbon atoms. The hydrocarbon group may be a straight-chain or branched, saturated or unsaturated hydrocarbon group, and is more preferably an alkylene group. Among these, a divalent hydrocarbon group having 2 carbon atoms is particularly preferred.

[0032] In formula (1), D is a stable bonding mode that does not easily cleave during LNP preparation or in blood. Specifically, it is an oxygen atom, an ester bond, a carbonate bond, or a carbamate bond. Here, an ester bond is "-O-C(O)-", a carbonate bond is "-O-C(O)-O-", a carbamate bond is "-O-C(O)-N-", a urea bond is "-N-C(O)-N-", and an amide bond is "N-C(O)-". Among these, an oxygen atom, a carbonate bond, or a carbamate bond is preferred, and a carbamate bond is particularly preferred.

[0033] In formula (1), E is a single bond or a divalent hydrocarbon group having 1 to 6 carbon atoms. The hydrocarbon group may be a linear or branched, saturated or unsaturated hydrocarbon group, and is more preferably an alkylene group. Among these, a divalent hydrocarbon group having 2 carbon atoms is particularly preferred.

[0034] In equation (1), G is an atomic group represented by the following equations (2a), (2b), (2c), (2d), (2e), or (2f). (In formulas (2a), (2b), (2c), (2d), (2e), and (2f), the wavy lines indicate bonding sites. In formula (2b), F is a fluorine atom. In formula (2f), Ts is a tosyl group.)

[0035] In a preferred embodiment, G is an atomic group represented by formula (2e).

[0036] An example of a method for producing the alkyne group-containing polyalkylene glycol lipid of the present invention is shown below, but the method for producing the lipid is not limited thereto and can be produced using general chemical reactions and purification methods that can be envisioned by those skilled in the art. Furthermore, it can be appropriately modified depending on the type of substituent, etc., and produced by any method that suits it. Among the production methods shown below, Method 1 is particularly preferred.

[0037] (Method 1)

[0038] In the formula, n is 21 to 226, R is a linear or branched, saturated or unsaturated hydrocarbon group having 14 to 21 carbon atoms, E is a single bond or a hydrocarbon group having 1 to 6 carbon atoms, G is an atomic group represented by the following formula (2c) or formula (2e), and Y is one of the four functional groups listed in the following formula (c).

[0039] (Formula (c)):

[0040]

[0041] Referring to Method 1, compound (I) is reacted with compound (II) to obtain compound (III). Compound (III), compound (IV), and a base (e.g., potassium tert-butoxide) are treated. The crude product is reacted with an acid (e.g., phosphoric acid (V)) to obtain compound (VI). Compound (VI) is then subjected to RCO ２ Compound (VII) is treated with H(VII), DMAP(4-dimethylaminopyridine), and a condensing agent (e.g., N,N'-dicyclohexylcarbodiimide) to obtain compound (VIII). Compound (VIII) is then treated with hydrogen(IX) and a catalyst (e.g., palladium carbon) to obtain compound (X). Compound (X) is reacted with compound (XI) (e.g., N,N'-disuccinimidyl carbonate) to obtain compound (XII). Compound (XII) is treated with compound (XIII) to obtain compound (XIV).

[0042] Compounds (I) and (II) used as raw materials may be purchased commercially or manufactured according to methods familiar to those skilled in the art.

[0043] (Method 2)

[0044] In the formula, n is 21 to 226, R is a linear or branched, saturated or unsaturated hydrocarbon group having 14 to 21 carbon atoms, E is a hydrocarbon group having 1 to 4 carbon atoms, G is an atomic group represented by the following formulas (2a), (2b), or (2f), and Z is a carboxylic acid or an N-hydroxysuccinimide ester.

[0045] Referring to method 2, compound (I) is reacted with compound (II) to obtain compound (III). Compound (III), compound (IV), and a base (e.g., potassium tert-butoxide) are treated. The crude product is reacted with an acid (e.g., phosphoric acid (V)) to obtain compound (VI). Compound (VI) is then subjected to RCO ２ The compound (VIII) is treated with H(VII), DMAP, and a condensing agent (e.g., N,N'-dicyclohexylcarbodiimide) to obtain compound (VIII). Compound (VIII) is then treated with hydrogen (IX) and a catalyst (e.g., palladium carbon) to obtain compound (X). Compound (X), compound (XV), an azo compound (e.g., diisopropyl azodicarboxylic acid), and a phosphine (e.g., triphenylphosphine) are treated. The crude product is treated with hydrazine (XVI) to recover compound (XVII). Compound (XVII), compound (XVIII), a condensing agent (e.g., 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride), and DMAP to obtain compound (XIX).

[0046] Compounds (I) and (II) used as raw materials may be purchased commercially or manufactured according to methods familiar to those skilled in the art.

[0047] (Method 3)

[0048] In the formula, n is 21 to 226, R is a linear or branched, saturated or unsaturated hydrocarbon group having 14 to 21 carbon atoms, E is a hydrocarbon group having 0 to 6 carbon atoms, G is an atomic group represented by the following formula (2c) or formula (2d), and Y is any one of the four types of functional groups listed in the following formula (c).

[0049]

[0050] (Formula (c)):

[0051] Referring to Production Method 3, compound (I) is reacted with compound (II) to obtain compound (III). Compound (III), compound (IV) and a base (for example, potassium tert-butoxide) are treated. The crude product is reacted with an acid (for example, phosphoric acid (V)) to obtain compound (VI). Compound (VI) is reacted with RCO ２ H (VII), DMAP and a condensing agent (for example, N,N'-dicyclohexylcarbodiimide) to obtain compound (VIII). Then, compound (VIII) is treated with hydrogen (IX) and a catalyst (for example, palladium on carbon) to obtain compound (X). Compound (X), compound (XV), an azo compound (for example, diisopropyl azodicarboxylate) and a phosphine (for example, triphenylphosphine) are treated. The crude product is treated with hydrazine (XVI) to recover compound (XVII). Compound (XVII) is treated with compound (XX) to obtain compound (XXI).

[0052] It should be noted that compound (I) and compound (II) used as raw materials can be purchased as commercially available products, or can be produced according to methods familiar to those skilled in the art.

[0053] (Example 1) The following PEG lipid (A) was synthesized by Production Method 1. The following PEG lipid (A) belongs to formula (XIV) of Production Method 1, and also belongs to the polyoxyalkylene glycol lipid having an alkyne group of formula (1). In formula (1), R １ and R ２A is a stearoyl group, with k=1, l=0, m=1, k+l+m=2, A is an oxygen atom, B is an ethylene group, n is 76, C is an ethylene group, D is a carbamate bond, E is an ethylene group, and G is the atomic group of formula (2e).

[0054] (1) 3-hydropolyoxyethylene-1,2-di(stearoyl)-sn-glycerol (molecular weight 4005) (compound (X)) obtained by the method described in International Publication No. 2022 / 065263 or a similar method was mixed with toluene (1.7 mL) and 2,6-di-tert-butyl-p-cresol (1 mg, 1000 ppm) and stirred at 50°C until dissolved. Then, di(N-succinimidyl) carbonate (compound (XI): 96 mg, 0.38 mmol) and pyridine (49 μL, 0.50 mmol) were added and the mixture was reacted at 80°C for 2 hours. The reaction solution was then cooled to room temperature, the insoluble components were filtered off, and the filtrate was concentrated. Next, the concentrate was dissolved in chloroform (2.7 mL) and washed twice with saline solution (4.0 mL). Magnesium sulfate (0.5 g) was added to the chloroform layer, and the mixture was stirred at room temperature for at least 20 minutes. The mixture was then filtered, and the filtrate was concentrated. Next, hexane (12.1 mL) was added to the concentrate, and the mixture was stirred at room temperature for at least 20 minutes. The crystals were then filtered off to obtain 3-succinimidyloxycarbonylpoly(oxyethylene)-1,2-di(stearoyl)-sn-glycerol (molecular weight 4146) (compound (XII)) (0.8 g, yield 78 mol%). The NMR data of the product is shown below.

[0055] １ H-NMR (CDCl ３ ): δ0.88 (6H, t, J = 6.8Hz), 1.19-1.35 (56H, m), 1.58-1.61 (4H, m), 2.30 (4H, q, J = 7.4Hz), 2.84 (4H, s), 3.45-3.48 (1H, m), 3.57-3.83 (303H, m), 4.15 (1H, dd, J = 6.6Hz, 11.9Hz), 4.34 (1H, dd, J = 3.7Hz, 11.9Hz), 4.45-4.47 (2H, m), 5.18-5.23 (1H, m)

[0056] (2) 3-Succinimidyloxycarbonylpoly(oxyethylene)-1,2-di(stearoyl)-sn-glycerol (molecular weight 4146) (compound (XII)) (100 mg, 24.1 μmol) was dissolved in dichloromethane (100 μL) by stirring, then dibenzocyclooctinamine (compound (XIII): 8.6 mg, 31.3 μmol) was added and the mixture was reacted at room temperature for 1 hour. Next, dichloromethane (100 μL) was added, the mixture was quenched with 1N HCl aqueous solution (400 μL), and the layers were separated. Washing was then performed a total of three times by adding 1N HCl aqueous solution (400 μL). After concentrating the dichloromethane layer, crystallization was performed with ethyl acetate / MTBE = 3 / 7 (w / w) (1.0 g) and drying was carried out to obtain DBCOP PEG lipid (molecular weight 4343) (A) (compound (XIV): 87 mg, yield 83 mol%). The NMR data of the product is shown below.

[0057] １ H-NMR (CDCl ３ ): δ0.86 (6H, t, J = 6.9Hz), 1.18-1.34 (56H, m), 1.54-1.61 (4H, m), 1.88-1.96 (1H, m), 2.29 (4H, q, J = 7.4Hz), 2.51 (1H, ddd, J = 4.9Hz, 7.8Hz, 16.7Hz), 3.08-3.27 (2H, m), 3.43-3.47 (1H, m), 3.55-3.81 (303H, m), 4.08-4.15 (3H, m), 4.32 (1H, dd, J=3.4Hz, 11.9Hz), 5.09-5.13 (1H, m), 5.16-5.22 (1H, m), 5.30 (1H, t, J = 5.7Hz), 7.26-7.42 (8H, m), 7.65 (1H, d, J = 7.6Hz)

[0058] (Example 2) The following PEG lipid (D) was synthesized by the method described in Method 1.

[0059] (1) Using 3-hydropolyoxyethylene-1,2-di(palmitoyl)-sn-glycerol (molecular weight 3977) (compound (X)) (3.0 g, 0.75 mmol) obtained by the method described in International Publication No. 2022 / 065263 or a similar method, 3-succinimidyloxycarbonylpoly(oxyethylene)-1,2-di(palmitoyl)-sn-glycerol (molecular weight 4118) (compound (XII)) (2.5 g, yield 81 mol%) was obtained by the method described in Example 1 (1) or a similar method. The NMR data of the product is shown below.

[0060] １ H-NMR (CDCl ３ ): δ0.88 (6H, t, J = 6.8Hz), 1.19-1.35 (48H, m), 1.58-1.61 (4H, m), 2.30 (4H, q, J = 7.4Hz), 2.84 (4H, s), 3.45-3.48 (1H, m), 3.57-3.83 (303H, m), 4.15 (1H, dd, J = 6.6Hz, 11.9Hz), 4.34 (1H, dd, J = 3.7Hz, 11.9Hz), 4.45-4.47 (2H, m), 5.18-5.23 (1H, m)

[0061] (2) Using the 3-succinimidyloxycarbonylpoly(oxyethylene)-1,2-di(palmitoyl)-sn-glycerol (compound (XII)) (1.0 g, 0.24 mmol) obtained in the preceding paragraph (1), DBCO PEG lipid (molecular weight 4315) (D) (compound (XIV): 0.89 g, yield 85 mol%) was obtained by the method described in (2) of Example 1 or a similar method. The NMR data of the product is shown below.

[0062] １ H-NMR (CDCl ３): δ0.86 (6H, t, J=6.9Hz), 1.18-1.34 (48H, m), 1.54-1.61 (4H, m), 1.88-1.96 (1H, m), 2.29 (4H, q, J = 7.4Hz), 2.51 (1H, ddd, J = 4.9Hz, 7.8Hz, 16.7Hz), 3.08-3.27 (2H, m), 3.43-3.47 (1H, m), 3.55-3.81 (303H, m), 4.08-4.15 (3H, m), 4.32 (1H, dd, J = 3.4Hz, 11.9Hz), 5.09-5.13 (1H, m), 5.16-5.22 (1H, m), 5.30 (1H, t, J = 5.7Hz), 7.26-7.42 (8H, m), 7.65 (1H, d, J = 7.6Hz)

[0063] (Example 3) The following PEG lipid (G) was synthesized according to Method 1.

[0064] (1) Using 3-hydropolyoxyethylene-1,2-di(arachidinoyl)-sn-glycerol (molecular weight 4033) (compound (X)) (5.0 g, 1.24 mmol) obtained by the method described in International Publication No. 2022 / 065263 or a similar method, 3-succinimidyloxycarbonylpoly(oxyethylene)-1,2-di(arachidinoyl)-sn-glycerol (molecular weight 4174) (compound (XII)) (3.9 g, yield 75 mol%) was obtained by the method described in Example 11-(1) or a similar method. The NMR data of the product is shown below.

[0065] １ H-NMR (CDCl ３ ): δ0.88 (6H, t, J = 6.8Hz), 1.19-1.35 (64H, m), 1.58-1.61 (4H, m), 2.30 (4H, q, J = 7.4Hz), 2.84 (4H, s), 3.45-3.48 (1H, m), 3.57-3.83 (303H, m), 4.15 (1H, dd, J = 6.6Hz, 11.9Hz), 4.34 (1H, dd, J = 3.7Hz, 11.9Hz), 4.45-4.47 (2H, m), 5.18-5.23 (1H, m)

[0066] (2) Using the 3-succinimidyloxycarbonylpoly(oxyethylene)-1,2-di(arachidinoyl)-sn-glycerol (compound (XII)) (2.5 g, 0.60 mmol) obtained in the preceding paragraph (1), DBCO PEG lipid (molecular weight 4371) (G) (compound (XIV): 2.1 g, yield 79 mol%) was obtained by the method described in Example 11-(2) or a similar method. The NMR data of the product is shown below.

[0067] １ H-NMR (CDCl ３ ): δ0.86 (6H, t, J=6.9Hz), 1.18-1.34 (64H, m), 1.54-1.61 (4H, m), 1.88-1.96 (1H, m), 2.29 (4H, q, J = 7.4Hz), 2.51 (1H, ddd, J = 4.9Hz, 7.8Hz, 16.7Hz), 3.08-3.27 (2H, m), 3.43-3.47 (1H, m), 3.55-3.81 (303H, m), 4.08-4.15 (3H, m), 4.32 (1H, dd, J = 3.4Hz, 11.9Hz), 5.09-5.13 (1H, m), 5.16-5.22 (1H, m), 5.30 (1H, t, J = 5.7Hz), 7.26-7.42 (8H, m), 7.65 (1H, d, J = 7.6Hz)

[0068] (Example 4) PEG lipid (J) was synthesized according to Method 1.

[0069] (1) Using 3-hydropolyoxyethylene-1,2-di(stearoyl)-sn-glycerol (molecular weight 2605) (compound (X)) (4.0 g, 1.54 mmol) obtained by the method described in International Publication No. 2022 / 065263 or a similar method, 3-succinimidyloxycarbonylpoly(oxyethylene)-1,2-di(stearoyl)-sn-glycerol (molecular weight 2746) (compound (XII)) (3.6 g, yield 86 mol%) was obtained by the method described in Example 1 (1) or a similar method. The NMR data of the product is shown below.

[0070] １ H-NMR (CDCl ３): δ0.88 (6H, t, J = 6.8Hz), 1.19-1.35 (56H, m), 1.58-1.61 (4H, m), 2.30 (4H, q, J = 7.4Hz), 2.84 (4H, s), 3.45-3.48 (1H, m), 3.57-3.83 (175H, m), 4.15 (1H, dd, J = 6.6Hz, 11.9Hz), 4.34 (1H, dd, J = 3.7Hz, 11.9Hz), 4.45-4.47 (2H, m), 5.18-5.23 (1H, m)

[0071] (2) Using the 3-succinimidyloxycarbonylpoly(oxyethylene)-1,2-di(stearoyl)-sn-glycerol (compound (XII)) (2.5 g, 0.91 mmol) obtained in the preceding paragraph (1), DBCO PEG lipid (molecular weight 2943) (J) (compound (XIV): 2.2 g, yield 82 mol%) was obtained by the method described in (2) of Example 1 or a similar method. The NMR data of the product is shown below.

[0072] １ H-NMR (CDCl ３ ): δ0.86 (6H, t, J=6.9Hz), 1.18-1.34 (56H, m), 1.54-1.61 (4H, m), 1.88-1.96 (1H, m), 2.29 (4H, q, J = 7.4Hz), 2.51 (1H, ddd, J = 4.9Hz, 7.8Hz, 16.7Hz), 3.08-3.27 (2H, m), 3.43-3.47 (1H, m), 3.55-3.81 (175H, m), 4.08-4.15 (3H, m), 4.32 (1H, dd, J = 3.4Hz, 11.9Hz), 5.09-5.13 (1H, m), 5.16-5.22 (1H, m), 5.30 (1H, t, J = 5.7Hz), 7.26-7.42 (8H, m), 7.65 (1H, d, J = 7.6Hz)

[0073] (Example 5) The following PEG lipid (M) was synthesized according to Method 1.

[0074] (1) Using 3-hydropolyoxyethylene-1,2-di(stearoyl)-sn-glycerol (molecular weight 5605) (compound (X)) (8.0 g, 1.43 mmol) obtained by the method described in International Publication No. 2022 / 065263 or a similar method, 3-succinimidyloxycarbonylpoly(oxyethylene)-1,2-di(stearoyl)-sn-glycerol (molecular weight 5746) (compound (XII)) (6.2 g, yield 75 mol%) was obtained by the method described in Example 1 (1) or a similar method. The NMR data of the product is shown below.

[0075] １ H-NMR (CDCl ３ ): δ0.88 (6H, t, J = 6.8Hz), 1.19-1.35 (56H, m), 1.58-1.61 (4H, m), 2.30 (4H, q, J = 7.4Hz), 2.84 (4H, s), 3.45-3.48 (1H, m), 3.57-3.83 (447H, m), 4.15 (1H, dd, J = 6.6Hz, 11.9Hz), 4.34 (1H, dd, J = 3.7Hz, 11.9Hz), 4.45-4.47 (2H, m), 5.18-5.23 (1H, m)

[0076] (2) Using the 3-succinimidyloxycarbonylpoly(oxyethylene)-1,2-di(stearoyl)-sn-glycerol (compound (XII)) (5.0 g, 0.87 mmol) obtained in the preceding paragraph (1), DBCO PEG lipid (molecular weight 5943) (M) (compound (XIV): 4.0 g, yield 77 mol%) was obtained by the method described in (2) of Example 1 or a similar method. The NMR data of the product is shown below.

[0077] １ H-NMR (CDCl ３): δ0.86 (6H, t, J = 6.9Hz), 1.18-1.34 (56H, m), 1.54-1.61 (4H, m), 1.88-1.96 (1H, m), 2.29 (4H, q, J = 7.4Hz), 2.51 (1H, ddd, J=4.9Hz, 7.8Hz, 16.7Hz), 3.08-3.27 (2H, m), 3.43-3.47 (1H, m), 3.55-3.81 (447H, m), 4.08-4.15 (3H, m), 4.32 (1H, dd, J=3.4Hz, 11.9Hz), 5.09-5.13 (1H, m), 5.16-5.22 (1H, m), 5.30 (1H, t, J = 5.7Hz), 7.26-7.42 (8H, m), 7.65 (1H, d, J = 7.6Hz)

[0078] (Example 6) The following PEG lipids (P) were synthesized according to Method 1.

[0079] (1) Using 3-hydropolyoxyethylene-1,2-di(stearoyl)-sn-glycerol (molecular weight 10605) (compound (X)) (10.0 g, 0.94 mmol) obtained by the method described in International Publication No. 2022 / 065263 or a similar method, 3-succinimidyloxycarbonylpoly(oxyethylene)-1,2-di(stearoyl)-sn-glycerol (molecular weight 10746) (compound (XII)) (7.2 g, yield 71 mol%) was obtained by the method described in Example 1 (1) or a similar method. The NMR data of the product is shown below.

[0080] １ H-NMR (CDCl ３ ): δ0.88 (6H, t, J = 6.8Hz), 1.19-1.35 (56H, m), 1.58-1.61 (4H, m), 2.30 (4H, q, J = 7.4Hz), 2.84 (4H, s), 3.45-3.48 (1H, m), 3.57-3.83 (903H, m), 4.15 (1H, dd, J = 6.6Hz, 11.9Hz), 4.34 (1H, dd, J = 3.7Hz, 11.9Hz), 4.45-4.47 (2H, m), 5.18-5.23 (1H, m)

[0081] (2) Using the 3-succinimidyloxycarbonylpoly(oxyethylene)-1,2-di(stearoyl)-sn-glycerol (compound (XII)) (5.0 g, 0.47 mmol) obtained in the preceding paragraph (1), DBCO PEG lipid (molecular weight 10943) (P) (compound (XIV): 3.9 g, yield 76 mol%) was obtained by the method described in Example 1 (2) or a similar method. The NMR data of the product is shown below.

[0082] １ H-NMR (CDCl ３ ): δ0.86 (6H, t, J=6.9Hz), 1.18-1.34 (56H, m), 1.54-1.61 (4H, m), 1.88-1.96 (1H, m), 2.29 (4H, q, J = 7.4Hz), 2.51 (1H, ddd, J = 4.9Hz, 7.8Hz, 16.7Hz), 3.08-3.27 (2H, m), 3.43-3.47 (1H, m), 3.55-3.81 (903H, m), 4.08-4.15 (3H, m), 4.32 (1H, dd, J = 3.4Hz, 11.9Hz), 5.09-5.13 (1H, m), 5.16-5.22 (1H, m), 5.30 (1H, t, J = 5.7Hz), 7.26-7.42 (8H, m), 7.65 (1H, d, J = 7.6Hz)

[0083] (Example 7) The following PEG lipid (Q) was synthesized by method 2. However, the following PEG lipid (Q) belongs to formula (XIX) of method 2 and also belongs to polyoxyalkylene glycol lipids having an alkyne group of formula (1). However, in formula (1), R １ and R ２ A is a stearoyl group, with k=1, l=0, m=1, k+l+m=2, A is an oxygen atom, B is an ethylene group, n is 76, C is an ethylene group, D is an amide bond, E is an ethylene group, and G is the atomic group of formula (2e).

[0084] (1) A toluene solution of 3-hydropolyoxyethylene-1,2-di(stearoyl)-sn-glycerol (molecular weight 4005) (compound (X): 20 g, 5.0 mmol), phthalimide (compound (XV): 0.88 g, 6.0 mmol), and triphenylphosphine (6.6 g, 25 mmol), obtained by the method described in International Publication No. 2022 / 065263 or a similar method, was cooled to 10°C, and diisopropyl azodicarboxylic acid (5.0 g, 25 mmol) was added. The mixture was stirred at room temperature for 1 hour, and methanol (1.0 mL) was added. After concentrating the solution, it was dissolved in toluene (218 mL) and methanol (95 mL). Ethylenediamine monohydrate (compound (XVI): 9.8 g, 125 mmol) was added at room temperature, and the mixture was stirred at 40°C for 4 hours. 200 mL of 25% aqueous sodium chloride solution was added, and after stirring at 60°C, the upper organic layer was recovered. The same procedure was repeated twice on the recovered organic layer, and then the organic layer was concentrated. The residue was subjected to silica gel column chromatography (eluent: ethyl acetate / methanol, chloroform / methanol) to obtain 3-[2-aminoethylpoly(oxyethylene)]-1,2-di(stearoyl)-sn-glycerol (molecular weight 4004) (compound (XVII): 7.0 g, yield 35 mol%). The NMR data of the product is shown below.

[0085] １ H-NMR (CDCl ３ ): δ0.88 (6H, t, J = 6.8Hz), 1.16-1.38 (56H, m), 1.54-1.68 (4H, m), 2.30 (4H, q, J = 7.3Hz), 2.88 (2H, t, J = 5.2Hz), 3.43-3.50 (2H, m), 3.53-3.90 (302H, m), 4.15 (1H, dd, J = 6.5Hz, 11.9Hz), 4.34 (1H, dd, J = 3.4Hz, 11.9Hz), 5.16-5.26 (1H, m)

[0086] ​(2) To the 3-[2-aminoethylpoly(oxyethylene)]-1,2-di(stearoyl)-sn-glycerol (molecular weight 4004) (compound (XVII): 1.0 g, 0.25 mmol) obtained in the preceding paragraph (1), chloroform (3.4 mL), dibenzocyclooctinic acid (compound (XVIII): 0.11 g, 0.38 mmol), 4-dimethylaminopyridine (3.1 mg, 25 μmol), triethylamine (70 mg, 0.50 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.12 g, 0.63 mmol) were added and the mixture was stirred at room temperature for 3 hours. Then, chloroform (3.4 mL) and 2% citric acid aqueous solution (10 mL) were added and the mixture was stirred at 10°C, after which the lower chloroform layer was collected. The same procedure was repeated four times on the collected chloroform layer, and then the chloroform layer was concentrated. The residue was subjected to silica gel column chromatography (eluent: chloroform / methanol) to obtain PEG lipid (molecular weight 4327) (Q) (compound (XIX): 0.81 g, yield 75 mol%). The NMR data of the product is shown below.

[0087] １ H-NMR (CDCl ３ ): δ0.86 (6H, t, J=6.9Hz), 1.18-1.34 (56H, m), 1.54-1.61 (4H, m), 1.88-1.96 (1H, m), 2.29 (4H, q, J = 7.4Hz), 2.51-2.56 (3H, m), 3.43-3.47 (1H, m), 3.55-3.81 (310H, m), 4.08-4.15 (1H, dd, J = 6.5Hz, 11.9Hz), 4.32 (1H, dd, J=3.4Hz, 11.9Hz), 5.09-5.13 (1H, m), 5.16-5.22 (1H, m), 5.30 (1H, t, J = 5.7Hz), 7.26-7.42 (7H, m), 7.65 (1H, d, J = 7.6Hz)

[0088] (Example 8) The following PEG lipids (R) were synthesized by method 2. However, PEG lipids (R) belong to polyoxyalkylene glycol lipids having an alkyne group of formula (1). In formula (1), R １ and R ２ ​A is a stearoyl group, with k=1, l=0, m=1, k+l+m=2, A is an oxygen atom, B is an ethylene group, n is 76, C is an ethylene group, D is an amide bond, E is a methylene group, and G is the atomic group of formula (2a).

[0089] To the 3-[2-aminoethylpoly(oxyethylene)]-1,2-di(stearoyl)-sn-glycerol (molecular weight 4004) (compound (XVII): 1.0 g, 0.25 mmol) obtained in Example 7 (1), chloroform (3.4 mL), 2-(cyclooct-2-yn-1-yloxy) acetate acid (compound (XVIII): 69 mg, 0.38 mmol), 4-dimethylaminopyridine (3.1 mg, 25 μmol), triethylamine (70 mg, 0.50 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.12 g, 0.63 mmol) were added and the mixture was stirred at room temperature for 3 hours. Then, chloroform (3.4 mL) and 2% citric acid aqueous solution (10 mL) were added, and after stirring at 10°C, the lower chloroform layer was collected. The same procedure was repeated four times on the recovered chloroform layer, and then the chloroform layer was concentrated. The residue was subjected to silica gel column chromatography (eluent: chloroform / methanol) to obtain PEG lipid (molecular weight 4204) (R) (compound (XIX): 0.75 g, yield 71 mol%). The NMR data of the product is shown below.

[0090] １ H-NMR (CDCl ３ ): δ0.86 (6H, t, J=6.9Hz), 1.18-1.34 (60H, m), 1.46-1.47 (3H, m), 1.54-1.61 (4H, m), 1.71-1.73 (1H, m), 1.97-2.00 (2H, m), 2.29 (4H, q, J = 7.4Hz), 3.43-3.47 (1H, m), 3.55-3.81 (310H, m), 4.08-4.15 (1H, dd, J = 6.5Hz, 11.9Hz), 4.26-4.32 (3H, m), 5.16-5.22 (1H, m), 5.30 (1H, t, J = 5.7Hz)

[0091] ​(Example 9) The following PEG lipid (S) was synthesized by method 2. However, PEG lipid (S) belongs to the polyoxyalkylene glycol lipid having an alkyne group of formula (1). In formula (1), R １ and R ２ A is a stearoyl group, with k=1, l=0, m=1, k+l+m=2, A is an oxygen atom, B is an ethylene group, n is 76, C is an ethylene group, D is an amide bond, E is a methylene group, and G is the atomic group of formula (2b).

[0092] To the 3-[2-aminoethylpoly(oxyethylene)]-1,2-di(stearoyl)-sn-glycerol (molecular weight 4004) (compound (XVII): 1.0 g, 0.25 mmol) obtained in Example 7 (1), chloroform (3.4 mL), 2-(2,2-difluorocyclooct-3-yn-1-yl) acetate acid (compound (XVIII): 77 mg, 0.38 mmol), 4-dimethylaminopyridine (3.1 mg, 25 μmol), triethylamine (70 mg, 0.50 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.12 g, 0.63 mmol) were added and the mixture was stirred at room temperature for 3 hours. Subsequently, chloroform (3.4 mL) and 2% citric acid aqueous solution (10 mL) were added, and after stirring at 10°C, the lower chloroform layer was collected. The same procedure was repeated four times on the collected chloroform layer, and then the chloroform layer was concentrated. The residue was subjected to silica gel column chromatography (eluent: chloroform / methanol) to obtain PEG lipid (molecular weight 4224) (S) (compound (XIX): 0.70 g, yield 66 mol%). The NMR data of the product is shown below.

[0093] １ H-NMR (CDCl ３ ​): δ0.86 (6H, t, J=6.9Hz), 1.13-1.38 (60H, m), 1.45-1.48 (2H, m), 1.54-1.61 (4H, m), 1.97-1.99 (2H, m), 2.19-2.21 (1H, m), 2.27-2.30 (6H, m), 3.43-3.47 (1H, m), 3.55-3.81 (310H, m), 4.08-4.15 (1H, dd, J = 6.5Hz, 11.9Hz), 5.16-5.22 (1H, m), 5.30 (1H, t, J=5.7Hz)

[0094] (Example 10) The following PEG lipid (T) was synthesized by method 2. However, PEG lipid (T) belongs to the polyoxyalkylene glycol lipid having an alkyne group of formula (1). In formula (1), R １ and R ２ A is a stearoyl group, with k=1, l=0, m=1, k+l+m=2, A is an oxygen atom, B is an ethylene group, n is 76, C is an ethylene group, D is an amide bond, E is an ethylene group, and G is the atomic group of formula (2f).

[0095] To the 3-[2-aminoethylpoly(oxyethylene)]-1,2-di(stearoyl)-sn-glycerol (molecular weight 4004) (compound (XVII): 1.0 g, 0.25 mmol) obtained in Example 7 (1), chloroform (3.4 mL), N-succinoyl-N'-p-toluenesulfonyl-4,8-diazacyclononine (0.14 g, 0.38 mmol), 4-dimethylaminopyridine (compound (XVIII): 3.1 mg, 25 μmol), triethylamine (70 mg, 0.50 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.12 g, 0.63 mmol) were added and the mixture was stirred at room temperature for 3 hours. Then, chloroform (3.4 mL) and 2% citric acid aqueous solution (10 mL) were added, and after stirring at 10°C, the lower chloroform layer was collected. The same procedure was repeated four times on the recovered chloroform layer, and then the chloroform layer was concentrated. The residue was subjected to silica gel column chromatography (eluent: chloroform / methanol) to obtain PEG lipid (molecular weight 4400) (T) (compound (XIX): 0.71 g, yield 65 mol%). The NMR data of the product is shown below.

[0096] １ H-NMR (CDCl ３ ): δ0.86 (6H, t, J = 6.9Hz), 1.18-1.34 (56H, m), 1.54-1.61 (4H, m), 1.66-1.68 (1H, m), 2.29 (4H, q, J = 7.4Hz), 2.43-2.46 (7H, m), 3.15-3.17 (2H, m), 3.27-3.29 (2H, m), 3.43-3.47 (1H, m), 3.55-3.89 (314H, m), 4.08-4.15 (1H, dd, J = 6.5Hz, 11.9Hz), 4.32 (1H, dd, J = 3.4Hz, 11.9Hz), 5.16-5.22 (1H, m), 5.30 (1H, t, J = 5.7Hz), 7.38 (2H, d, J = 7.6Hz), 7.68 (2H, d, J = 7.6Hz)

[0097] ​(Example 11) The following PEG lipids (U) were synthesized by method 3. However, the following PEG lipids (U) belong to formula (XXI) of method 3 and also belong to polyoxyalkylene glycol lipids having an alkyne group of formula (1). However, in formula (1), R １ and R ２ A is a stearoyl group, with k=1, l=0, m=1, k+l+m=2, A is an oxygen atom, B is an ethylene group, n is 76, C is an ethylene group, D is a carbamate bond, E is a single bond, and G is the atomic group of formula (2d).

[0098] To the 3-[2-aminoethylpoly(oxyethylene)]-1,2-di(stearoyl)-sn-glycerol (molecular weight 4004) (compound (XVII): 1.0 g, 0.25 mmol) obtained in Example 7 (1), dichloromethane (1.0 mL) was added and stirred to dissolve, and then 4-nitrophenyl tricyclo[10.4.0.0 ４ , ９ ]hexadeca-1(16),4,6,8,12,14-hexaen-10-yn-2-yl carbonate (compound (XX): 0.13 g, 0.33 mmol) was added and reacted at room temperature for 1 hour. The reaction mixture was then concentrated, and the residue was subjected to silica gel column chromatography (eluent: chloroform / methanol) to obtain PEG lipid (molecular weight 4286) (U) (compound (XXI): 0.86 g, yield 80 mol%). The NMR data of the product is shown below.

[0099] １ H-NMR (CDCl ３ ​): δ0.86 (6H, t, J = 6.9Hz), 1.18-1.34 (56H, m), 1.46-1.48 (1H, m), 1.54-1.61 (4H, m), 1.71-1.73 (1H, m), 2.29 (4H, q, J = 7.4Hz), 3.43-3.47 (1H, m), 3.55-3.81 (310H, m), 4.08-4.15 (1H, dd, J=6.5Hz, 11.9Hz), 4.32 (1H, dd, J=3.4Hz, 11.9Hz), 5.16-5.22 (1H, m), 5.30 (1H, t, J = 5.7Hz), 7.26-7.42 (7H, m), 7.65 (1H, d, J = 7.6Hz)

[0100] (Example 12) The following PEG lipid (W) was synthesized by method 3. However, PEG lipid (W) belongs to the polyoxyalkylene glycol lipid having an alkyne group of formula (1). In formula (1), R １ and R ２ A is a stearoyl group, with k=1, l=0, m=1, k+l+m=2, A is an oxygen atom, B is an ethylene group, n is 76, C is an ethylene group, D is a carbamate bond, E is a methylene group, and G is the atomic group of formula (2c).

[0101] 3-[2-aminoethylpoly(oxyethylene)]-1,2-di(stearoyl)-sn-glycerol (molecular weight 4004) (compound (XVII): 1.0 g, 0.25 mmol) obtained in Example 7 (1) was dissolved by stirring with dichloromethane (1.0 mL), and then {bicyclo[6.1.0]non-4-yn-9-yl}methyl 2,5-dioxopyrrolidin-1-yl carbonate (compound (XX): 95 mg, 0.33 mmol) was added and the mixture was reacted at room temperature for 1 hour. The reaction mixture was then concentrated, and the residue was subjected to silica gel column chromatography (eluent: chloroform / methanol) to obtain PEG lipid (molecular weight 4216) (W) (compound (XXI): 0.87 g, yield 83 mol%). The NMR data of the product is shown below.

[0102] １ H-NMR (CDCl ３ ​): δ0.78-0.80 (3H, m), 0.86 (6H, t, J=6.9Hz), 1.18-1.34 (58H, m), 1.54-1.61 (6H, m), 1.92-1.94 (2H, m), 2.02-2.04 (2H, m), 2.29 (4H, q, J = 7.4Hz), 3.43-3.47 (1H, m), 3.55-3.81 (311H, m), 4.08-4.15 (1H, dd, J = 6.5Hz, 11.9Hz), 4.32 (1H, dd, J=3.4Hz, 11.9Hz), 5.16-5.22 (1H, m), 5.30 (1H, t, J=5.7Hz)

[0103] The polyalkylene glycol lipid having an alkyne group according to the present invention possesses both sufficient immobilization ability on the LNP surface and highly specific functional groups, making it useful as a base for LNPs with diverse organ-specific properties other than liver.

[0104] Although the present invention has been described in detail and with reference to specific embodiments, it will be apparent to those skilled in the art that various changes and modifications can be made without departing from the spirit and scope of the invention. This application is based on Japanese Patent Application No. 2025-049317 filed on 25 March 2025, the contents of which are incorporated herein by reference.

Claims

1. A polyalkylene glycol lipid characterized by being represented by the following formula (1). (In formula (1), R １ and R ２ Each of the following atoms is independently a hydrogen atom, an aliphatic hydrocarbon group having 15 to 22 carbon atoms, or an acyl group having 15 to 22 carbon atoms; k, l, and m are independently numbers satisfying 6 ≥ k ≥ 0, 6 ≥ l ≥ 0, 6 ≥ m ≥ 0, and k + l + m ≥ 2; A is an oxygen atom, an ester bond, a carbonate bond, or a carbamate bond; B is a divalent hydrocarbon group having 1 to 4 carbon atoms; n is a number from 21 to 226; C is a divalent hydrocarbon group having 1 to 4 carbon atoms; D is an oxygen atom, an ester bond, a carbonate bond, a carbamate bond, a urea bond, or an amide bond; E is a single bond or a divalent hydrocarbon group having 1 to 6 carbon atoms; and G is one of the atomic groups represented by the following formulas (2a), (2b), (2c), (2d), (2e), or (2f). (In formulas (2a), (2b), (2c), (2d), (2e), and (2f), the wavy lines indicate bonding sites. In formula (2b), F is a fluorine atom. In formula (2f), Ts is a tosyl group.) 2. In equation (1), R １ and R ２ The polyalkylene glycol lipid according to claim 1, characterized in that each of them is independently a linear, saturated acyl group having 15 to 20 carbon atoms.

3. The polyalkylene glycol lipid according to claim 1 or 2, characterized in that k and m are 1 and l is 0 in formula (1).

4. The polyalkylene glycol lipid according to claim 1 or 2, characterized in that A is an oxygen atom in formula (1).

5. The polyalkylene glycol lipid according to claim 1 or 2, characterized in that in formula (1), B is a divalent hydrocarbon group having 2 carbon atoms.

6. The polyalkylene glycol lipid according to claim 1 or 2, characterized in that in formula (1), C is a divalent hydrocarbon group having 2 carbon atoms.

7. The polyalkylene glycol lipid according to claim 1 or 2, characterized in that D in formula (1) is a carbamate bond.

8. The polyalkylene glycol lipid according to claim 1 or 2, characterized in that, in formula (1), E is a divalent hydrocarbon group having 2 carbon atoms.

9. The polyalkylene glycol lipid according to claim 1 or 2, characterized in that in formula (1), G is an atomic group represented by formula (2e).

10. A substrate for lipid nanoparticles, characterized by comprising the polyalkylene glycol lipid described in claim 1 or 2.

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