Protein transport material

Abstract

This protein transport material contains a polycyclic compound having, in the main skeleton, one or two structures represented by general formula (1) (In the formula, Ar1 represents a condensed aromatic ring optionally having a substituent with the proviso that when R is a group having a primary, secondary or tertiary amino group or R is a group having a nitrogen cation-containing group, Ar1 is a condensed aromatic ring that is other than a perylene diimide ring and optionally has a substituent; R represents an anionic group or a cationic group; n represents an integer of 1 or more; and when n is an integer of 2 or more, the n number of Rs may be the same or different.) or general formula (5) (In the formula, R17 and R18 are the same or different and each represent an aryl group optionally having a substituent.). The protein transport material uses precisely synthesizable small molecules, has excellent protein transport efficiency, and is capable of transporting a protein into cells.

Description

Protein transport materials

[0001] The present invention relates to protein transport materials.

[0002] Biopolymers such as proteins and nucleic acids are not only used in basic research, but in recent years have also shown promise as pharmaceuticals (antibody drugs, nucleic acid drugs, etc.) and genome editing tools. Direct protein delivery, in particular, does not require transcription, translation, or post-translational modification compared to nucleic acid-based protein expression. This makes it ideal for generating iPS cells and inducing cell differentiation, where the timing of functional expression is crucial. Additionally, protocols for introducing Cas9 proteins are commonly used in genome editing, and there is a growing demand for flexible control of protein delivery. However, biopolymers generally suffer from very low membrane permeability due to their size and surface charge. Proteins, in particular, have a more complex surface charge distribution than nucleic acids, so there are few reported delivery methods. While commercially available protein delivery materials are available, few, including the well-known commercial product PLUSin, can effectively deliver proteins into cells.

[0003] Methods for intracellular protein transport that have been reported to date include methods using microfluidic devices, membrane-permeable peptides, cell-derived vesicles, virus-like synthetic nanoparticles, lipid nanoparticles, inorganic nanoparticles, polymers, etc. In particular, with regard to methods using polymers, structure-function correlation studies have been conducted, and it is becoming clear that perfluoroalkyl groups (Non-Patent Documents 1-2), guanidyl groups (Non-Patent Documents 3-5), phenylboronic acid (Non-Patent Document 6), etc. are important structures for protein transport. However, this method has a short history, and the development of various transport carrier molecules is still required.

[0004] Biomaterials 2018, 182, 167-175.Nat. Commun. 2018, 9, 1377.Nano Lett. 2017, 17, 1678-1684.Biomacromolecules 2017, 18, 8190-825.Bioconjugate Chem. 2018, 29, 2679-2690.Sci. Adv. 2019, 5, eaaw8922.

[0005] The present invention aims to solve the above-mentioned problems and to provide a protein transport material that uses small molecules that can be precisely synthesized, has excellent protein transport efficiency, and is capable of transporting proteins into cells.

[0006]

[0009] In view of the above object, the present inventors conducted extensive research and found that polycyclic aromatic compounds having specific structures are small molecules that can be precisely synthesized, have excellent protein transport efficiency, and are capable of transporting proteins into cells. That is, the present invention encompasses the following features.

[0007] Item 1. A protein transport material containing a polycyclic compound, wherein the polycyclic compound is represented by general formula (1):

[0008]

[0009] [In the formula, Ar １ represents a fused aromatic ring which may have a substituent, provided that when R is a group having a primary, secondary or tertiary amino group; or a group having a nitrogen cation-containing group, Ar １ is a fused aromatic ring other than a perylene diimide ring which may have a substituent. R represents an anionic group or a cationic group. n represents an integer of 1 or more. When n is an integer of 2 or more, the n Rs may be the same or different.] or is represented by general formula (5):

[0010]

[0011] [In the formula, R １７ and R １８and each of the anionic group or cationic group in the general formula (1) is represented by the general formula (2A) or (2B):

[0012]

[0013] [In the formula, Ar ２ represents an aromatic ring which may have a substituent. ３ and R ４ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar ２ represents an aromatic ring other than a perylene diimide ring which may have a substituent. ３ represents a nitrogen-containing heterocycle which may have a substituent, provided that R ３ and R ４ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar ３ R is a nitrogen-containing heterocycle other than a perylene diimide ring which may have a substituent. ３ represents a carboxy group; a primary, secondary, or tertiary amino group; a nitrogen cation-containing group; a sulfo group; a phosphate group; an ammonium group; a phosphonium group; or a sulfonium group. ４ represents a hydrogen atom or a hydrocarbon group; and Y represents a bond or a divalent group.

[0014] Item 2. The polycyclic compound represented by the general formula (1) is represented by the general formula (1A):

[0015]

[0016] [In the formula, Ar １ represents a fused aromatic ring which may have a substituent. １ and R ２ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar １ R is a fused aromatic ring other than a perylene diimide ring which may have a substituent. １ and R ２are the same or different and represent an anionic group or a cationic group.], and the anionic group or the cationic group in the general formula (1A) is represented by the general formula (2A) or (2B):

[0017]

[0018] [In the formula, Ar ２ represents an aromatic ring which may have a substituent. ３ and R ４ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar ２ represents an aromatic ring other than a perylene diimide ring which may have a substituent. ３ represents a nitrogen-containing heterocycle which may have a substituent, provided that R ３ and R ４ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar ３ R is a nitrogen-containing heterocycle other than a perylene diimide ring which may have a substituent. ３ represents a carboxy group; a primary, secondary, or tertiary amino group; a nitrogen cation-containing group; a sulfo group; a phosphate group; an ammonium group; a phosphonium group; or a sulfonium group. ４ represents a hydrogen atom or a hydrocarbon group; and Y represents a bond or a divalent group.

[0019] Item 3. The group represented by general formula (2A) is a group represented by general formula (2A'):

[0020]

[0021] [In the formula, Ar ２ and Y is the same as above. Item 3. The protein transport material according to Item 2, wherein the group is represented by the formula:

[0022] Item 4. Said Ar １ Item 4. The protein transport material according to any one of Items 1 to 3, wherein is a fused aromatic hydrocarbon ring.

[0023] Item 5. Said R ３is a carboxy group, a primary amino group, an optionally substituted imidazolium group, an optionally substituted pyridinium group, an optionally substituted tetraalkylammonium group, or an optionally substituted triazolium group.

[0024] Item 6. Ar in the general formula (1) １ Item 6. The protein transport material according to any one of Items 1 to 5, wherein the number of fused aromatic rings as the ring unit is 2 to 10.

[0025] Item 7. The polycyclic compound having one or two structures represented by the general formula (5) in the main skeleton is a polycyclic compound represented by the general formula (5'):

[0026]

[0027] [In the formula, R １７ and R １８ R may be the same or different and represent an aryl group which may have a substituent. １９ , R ２０ , R ２１ and R ２２ are the same or different and represent a hydrogen atom, an alkyl group which may have a substituent, or an aryl group which may have a substituent. １９ and R ２０ , R ２０ and R ２１ , and R ２１ and R ２２ are joined together to form an aromatic ring at at least one position, and may be joined together to form a ring at other positions.]

[0028] Item 8. In the general formula (5′), R １９ and R ２０ , R ２０ and R ２１ , and R ２１ and R ２２ Item 8. The protein transport material according to Item 7, wherein the number of aromatic rings formed at at least one site is 1 to 10.

[0029] Item 9. The protein transport material according to any one of Items 1 to 8, further comprising a physiological buffer solution having a pH of 6.0 to 8.0.

[0030] Item 10. The protein transport material according to any one of Items 1 to 9, which is a protein transport material for transporting proteins to at least one cell selected from the group consisting of mammalian cells, plant cells, insect cells, and Escherichia coli.

[0031] Item 11. A pharmaceutical composition comprising the protein transport material according to any one of Items 1 to 10 and a protein.

[0032] Item 12. A genome editing composition comprising the protein transport material according to any one of Items 1 to 10 and a protein.

[0033] Item 13. General formula (1'):

[0034]

[0035] [In the formula, Ar １ R' represents a fused aromatic ring which may have a substituent. R' represents a group represented by general formula (2A'):

[0036]

[0037] (In the formula, Ar ２ represents an aromatic ring which may have a substituent. Y represents a bond or a divalent group. ) represents a group represented by the following formula: n represents an integer of 1 or more. When n is an integer of 2 or more, the n Rs may be the same or different. ] or is represented by the following formula (5'):

[0038]

[0039] [In the formula, R １７ and R １８ R may be the same or different and represent an aryl group which may have a substituent. １９ , R ２０ , R ２１ and R ２２ are the same or different and represent a hydrogen atom, an alkyl group which may have a substituent, or an aryl group which may have a substituent. １９ and R ２０ , R ２０ and R ２１ , and R２１ and R ２２ are joined together to form an aromatic ring at at least one position, and may be joined together to form a ring at other positions.

[0040] Item 14. The polycyclic compound represented by the general formula (1) is represented by the general formula (1A'):

[0041]

[0042] [In the formula, Ar １ represents a fused aromatic ring which may have a substituent. １’ and R ２’ are the same or different and are represented by the general formula (2A'):

[0043]

[0044] (In the formula, Ar ２ Item 14. The polycyclic compound according to item 13, wherein: Y represents a bond or a divalent group;

[0045] Item 15. The polycyclic compound represented by the general formula (1′) is a polycyclic compound represented by the general formula (1A1′):

[0046]

[0047] [In the formula, R １ ' and R ２ ' are the same or different and represent a group represented by the general formula (2A'):

[0048]

[0049] (In the formula, Ar ２ represents an aromatic ring which may have a substituent; Y represents a bond or a divalent group. ５ , R ６ , R ７ and R ８ are the same or different and represent a hydrogen atom, a hydroxyl group, a halogen atom, an alkyl group, an alkoxy group, an aryl group, or an alkoxycarbonyl group. ５ , R ６ , R ７ and R ８and at least one of the groups represents a hydroxyl group, an alkoxy group, or an alkoxycarbonyl group.

[0050] According to the present invention, it is possible to provide a protein transport material that is excellent in protein transport efficiency and capable of transporting proteins into cells, using small molecules that can be precisely synthesized.

[0051] The following shows the results of a fluorescent protein R-PE transport test in Test Example 1. The following shows the results of a hydrolase β-galactosidase transport test (part 1) in Test Example 2. The following shows the results of a fluorescently labeled antibody transport test in Test Example 3. The following shows the results of a trypsin transport test in Test Example 4. The following shows the results of a hydrolase β-galactosidase transport test (part 2) in Test Example 5.

[0052] In this specification, the term "containing" is a concept that encompasses all of "comprise," "consist essentially of," and "consist only of."

[0053] In addition, in this specification, when a numerical range is expressed as "A to B," it means A or more and B or less.

[0054] 1. Protein Transport Material The protein transport material of the present invention is a protein transport material containing a polycyclic compound, and the polycyclic compound is represented by the general formula (1):

[0055]

[0056] [In the formula, Ar １ represents a fused aromatic ring which may have a substituent, provided that when R is a group having a primary, secondary or tertiary amino group; or a group having a nitrogen cation-containing group, Ar １ is a fused aromatic ring other than a perylene diimide ring which may have a substituent. R represents an anionic group or a cationic group. n represents an integer of 1 or more. When n is an integer of 2 or more, the n Rs may be the same or different.] or is represented by general formula (5):

[0057]

[0058] [In the formula, R １７ and R １８ and each of the anionic group or cationic group in the general formula (1) is represented by the general formula (2A) or (2B):

[0059]

[0060] [In the formula, Ar ２ represents an aromatic ring which may have a substituent. ３ and R ４ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar ２ represents an aromatic ring other than a perylene diimide ring which may have a substituent. ３ represents a nitrogen-containing heterocycle which may have a substituent, provided that R ３ and R ４ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar ３ R is a nitrogen-containing heterocycle other than a perylene diimide ring which may have a substituent. ３ represents a carboxy group; a primary, secondary, or tertiary amino group; a nitrogen cation-containing group; a sulfo group; a phosphate group; an ammonium group; a phosphonium group; or a sulfonium group. ４ represents a hydrogen atom or a hydrocarbon group, and Y represents a bond or a divalent group.

[0061] (1-1) Polycyclic Compound (General Formula (1)) A polycyclic compound is a compound composed of fused aromatic rings which may have a substituent, and as described above, means a compound represented by general formula (1).

[0062] In the general formula (1), n ​​represents an integer of 1 or more. １Although this may vary depending on the number of aromatic rings possessed by n, from the viewpoints of ease of precision synthesis, ease of improving protein transport efficiency, and ease of transporting proteins into cells, n is preferably an integer of 1 to 5, more preferably an integer of 2 to 4, even more preferably 2 or 3, and particularly preferably 2.

[0063] Therefore, the polycyclic compound represented by general formula (1) used in the protein transport material of the present invention is represented by general formula (1A):

[0064]

[0065] [In the formula, Ar １ represents a fused aromatic ring which may have a substituent. １ and R ２ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar １ R is a fused aromatic ring other than a perylene diimide ring which may have a substituent. １ and R ２ are the same or different and represent an anionic group or a cationic group.], and the anionic group or the cationic group in the general formula (1A) is represented by the general formula (2A) or (2B):

[0066]

[0067] [In the formula, Ar ２ represents an aromatic ring which may have a substituent. ３ and R ４ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar ２ represents an aromatic ring other than a perylene diimide ring which may have a substituent. ３ represents a nitrogen-containing heterocycle which may have a substituent, provided that R ３ and R ４ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar ３ R is a nitrogen-containing heterocycle other than a perylene diimide ring which may have a substituent. ３represents a carboxy group; a primary, secondary, or tertiary amino group; a nitrogen cation-containing group; a sulfo group; a phosphate group; an ammonium group; a phosphonium group; or a sulfonium group. ４ represents a hydrogen atom or a hydrocarbon group, and Y represents a bond or a divalent group.] is preferred.

[0068] The fused aromatic rings constituting the polycyclic compound represented by general formula (1) used in the protein transport material of the present invention, that is, Ar in general formulas (1) and (1A), １ The number of rings contained in the fused aromatic ring represented by the formula (I) is not particularly limited, but from the viewpoints of ease of precision synthesis, ease of improving protein transport efficiency, and ease of transporting proteins into cells, it is preferably 2 to 10, more preferably 3 to 8, and even more preferably 4 to 6.

[0069] The fused aromatic ring constituting the polycyclic compound represented by general formula (1) used in the protein transport material of the present invention is not particularly limited as long as it is a fused aromatic ring, and both a fused aromatic hydrocarbon ring and a fused heteroaromatic ring can be used (however, R １ and R ２ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar １ is a fused aromatic ring other than a perylene diimide ring which may have a substituent), but a fused aromatic hydrocarbon ring is preferred from the viewpoints of ease of precision synthesis, ease of improving protein transport efficiency, and ease of transporting proteins into cells. Specific examples of such fused aromatic rings include a naphthalene ring, a pentalene ring, an indene ring, an anthracene ring, a phenanthrene ring, a tetracene ring, a pyrene ring, a chrysene ring, a triphenylene ring, a fluoranthene ring, a dibenzopentalene ring, a pentacene ring, a perylene ring, a benzopyrene ring, a coronene ring, and a corannulene ring.

[0070] The fused aromatic rings constituting the polycyclic compound represented by general formula (1) used in the protein transport material of the present invention, that is, Ar in general formulas (1) and (1A), １The fused aromatic ring represented by the formula (I) may have a substituent. The substituent is not particularly limited, and examples thereof include a hydroxyl group, a halogen atom (such as a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom), an alkyl group described below, an alkoxy group (such as a methoxy group, an ethoxy group, or an n-propoxy group), an aryl group described below, and an alkoxycarbonyl group (such as a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, or an n-butyloxycarbonyl group).

[0071] Considering that the protein transport material of the present invention is used to transport proteins, that is, is used in vivo, it is preferable to employ a substituent that can easily improve the solubility in physiological buffers, that is, that can easily improve water solubility. From this viewpoint, it is preferable to employ a substituent that can easily improve the solubility in physiological buffers, that is, that can easily improve water solubility, in general formulas (1) and (1A). １ The substituent of the fused aromatic ring represented by the formula (I) is preferably a hydroxyl group, an alkoxy group (a methoxy group, an ethoxy group, an n-propoxy group, etc.), an alkoxycarbonyl group (a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an n-butyloxycarbonyl group, etc.), or the like, more preferably a hydroxyl group, an alkoxycarbonyl group (a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an n-butyloxycarbonyl group, etc.), or the like, and even more preferably an alkoxycarbonyl group (a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an n-butyloxycarbonyl group, etc.), or the like.

[0072] When these substituents are present, the number of the substituents is not particularly limited, but from the viewpoints of facilitating precision synthesis and improving water solubility, the number of the substituents is preferably 1 to 10, more preferably 2 to 8, and even more preferably 3 to 6.

[0073] Examples of polycyclic compounds represented by general formula (1) having such fused aromatic rings as the protein transport material of the present invention include compounds represented by general formula (1A1) or (1A2):

[0074]

[0075] [In the formula, R １ , R ２ , R ９ , R １０, R １１ , R １２ and R １３ are the same or different and represent an anionic group or a cationic group. ５ , R ６ , R ７ and R ８ are the same or different and represent a hydrogen atom, a hydroxyl group, a halogen atom, an alkyl group, an alkoxy group, an aryl group, or an alkoxycarbonyl group. ５ , R ６ , R ７ and R ８ at least one of which represents a hydroxyl group, an alkoxy group, or an alkoxycarbonyl group.] is preferred.

[0076] In the compound (perylene compound) represented by the general formula (1A1), the substituent of the fused aromatic ring, that is, R ５ , R ６ , R ７ and R ８ represents a hydrogen atom, a hydroxyl group, a halogen atom (such as a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom), an alkyl group as described below, an alkoxy group (such as a methoxy group, an ethoxy group, or an n-propoxy group), an aryl group as described below, or an alkoxycarbonyl group (such as a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, or an n-butyloxycarbonyl group).

[0077] Considering that the protein transport material of the present invention is used to transport proteins, that is, is used in vivo, it is preferable to employ a substituent that can easily improve the solubility in physiological buffers, that is, that can easily improve water solubility. ５ , R ６ , R ７ and R ８is preferably a hydroxyl group, an alkoxy group (a methoxy group, an ethoxy group, an n-propoxy group, etc.), an alkoxycarbonyl group (a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an n-butyloxycarbonyl group, etc.), or the like, more preferably a hydroxyl group, an alkoxycarbonyl group (a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an n-butyloxycarbonyl group, etc.), or the like, and even more preferably an alkoxycarbonyl group (a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an n-butyloxycarbonyl group, etc.), or the like.

[0078] Similarly, from the viewpoint of ease of precision synthesis and ease of improving water solubility, in the compound represented by general formula (1A1) (perylene compound), R ５ , R ６ , R ７ and R ８ Among these, 1 to 4, preferably 2 to 4, more preferably 3 to 4 are preferably a hydroxyl group, an alkoxy group, an alkoxycarbonyl group, or the like, more preferably a hydroxyl group, an alkoxycarbonyl group, or the like, and even more preferably an alkoxycarbonyl group, or the like.

[0079] The anionic group or cationic group possessed by the polycyclic compound represented by general formula (1) in the protein transport material of the present invention is not particularly limited, but from the viewpoints of ease of precise synthesis and ease of improving water solubility, a group having a carboxy group; a group having a primary, secondary, or tertiary amino group; a group having a nitrogen cation-containing group; a group having a sulfo group; a group having a phosphate group; a group having an ammonium group; a group having a phosphonium group; a group having a sulfonium group, and the like are preferred. Among these, in the present invention, a group represented by general formula (2A) or (2B):

[0080]

[0081] [In the formula, Ar ２ represents an aromatic ring which may have a substituent. ３ and R ４ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar ２represents an aromatic ring other than a perylene diimide ring which may have a substituent. ３ represents a nitrogen-containing heterocycle which may have a substituent, provided that R ３ and R ４ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar ３ R is a nitrogen-containing heterocycle other than a perylene diimide ring which may have a substituent. ３ represents a carboxy group; a primary, secondary, or tertiary amino group; a nitrogen cation-containing group; a sulfo group; a phosphate group; an ammonium group; a phosphonium group; or a sulfonium group. ４ represents a hydrogen atom or a hydrocarbon group, and Y represents a bond or a divalent group.

[0082] The anionic group or cationic group (R, R in general formulas (1), (1A), and (1A1)) possessed by the polycyclic compound represented by general formula (1) as the protein transport material of the present invention is １ and R ２ and R in general formula (1A2) ９ , R １０ , R １１ , R １２ and R １３ a group having a carboxy group as R in general formula (2A); a group having a primary, secondary or tertiary amino group; a group having a nitrogen cation-containing group; a group having a sulfo group; a group having a phosphate group; a group having an ammonium group; a group having a phosphonium group; or a group having a sulfonium group; a carboxy group; a primary, secondary or tertiary amino group; a nitrogen cation-containing group; a sulfo group; a phosphate group; an ammonium group; a phosphonium group; or a sulfonium group (R in general formula (2A) ３In the above formula (I), examples of the primary, secondary, or tertiary amino group include, in addition to a primary amino group (unsubstituted amino group), alkylamino groups having 1 to 6 carbon atoms (preferably 1 to 4), such as an N-methylamino group, an N-ethylamino group, an N-n-propylamino group, or an N-isopropylamino group; dialkylamino groups having 2 to 10 carbon atoms (preferably 2 to 8), such as a dimethylamino group, a diethylamino group, a di(n-propyl)amino group, or a diisopropylamino group; and cyclic amino groups, such as a piperidino group or a piperazino group. Among these, from the viewpoints of ease of precision synthesis and ease of improving water solubility, primary amino groups (unsubstituted amino groups), an N-methylamino group, a piperidino group, a piperazino group, and the like are preferred, and primary amino groups (unsubstituted amino groups), a piperidino group, a piperazino group, and the like are more preferred.

[0083] The anionic group or cationic group (R, R in general formulas (1), (1A), and (1A1)) possessed by the polycyclic compound represented by general formula (1) as the protein transport material of the present invention is １ and R ２ and R in general formula (1A2) ９ , R １０ , R １１ , R １２ and R １３ a group having a carboxy group as R ; a group having a primary, secondary or tertiary amino group; a group having a nitrogen cation-containing group; a group having a sulfo group; a group having a phosphate group; a group having an ammonium group; a group having a phosphonium group; or a group having a sulfonium group; a carboxy group; a primary, secondary or tertiary amino group; or a nitrogen cation-containing group; a sulfo group; a phosphate group; an ammonium group; a phosphonium group; or a sulfonium group (R ３ In the above formula (I), examples of the nitrogen cation-containing group include an imidazolium group, a pyridinium group, a quaternary ammonium group, a tetraalkylammonium group, and a triazolium group. The alkyl groups in the tetraalkylammonium groups may be the same or different, and the alkyl groups described below can be used.

[0084] The nitrogen cation-containing group may have a substituent, and examples of the substituent that the nitrogen cation-containing group may have include a hydroxyl group, an alkoxy group (a methoxy group, an ethoxy group, an n-propoxy group, etc.), an alkoxycarbonyl group (a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an n-butyloxycarbonyl group, etc.), and the like.

[0085] When these substituents are present, the number of the substituents is not particularly limited, but may be, for example, 1 to 6, preferably 1 to 4, and more preferably 1 or 2.

[0086] In consideration of using the protein transport material of the present invention in a living body, it is preferable that the protein transport material of the present invention has as low toxicity as possible. For this reason, in the polycyclic aromatic compound represented by general formula (1), the anionic group or cationic group (R, R in general formulas (1), (1A), and (1A1)) is preferably substituted with a hydroxyl group. １ and R ２ and R in general formula (1A2) ９ , R １０ , R １１ , R １２ and R １３ a group having a carboxy group as R in general formula (2A); a group having a primary, secondary or tertiary amino group; a group having a nitrogen cation-containing group; a group having a sulfo group; a group having a phosphate group; a group having an ammonium group; a group having a phosphonium group; or a group having a sulfonium group; a carboxy group; a primary, secondary or tertiary amino group; a nitrogen cation-containing group; a sulfo group; a phosphate group; an ammonium group; a phosphonium group; or a sulfonium group (R in general formula (2A) ３ As the carboxy group, primary, secondary or tertiary amino group, nitrogen cation-containing group, sulfo group, phosphate group, ammonium group, phosphonium group, or sulfonium group constituting the carboxy group, or primary, secondary or tertiary amino group, preferred are the carboxy group, or primary, secondary or tertiary amino group. However, even when a nitrogen cation-containing group is used, it is possible to reduce toxicity by, for example, diluting the concentration.

[0087] In the general formula (2A), Ar ２The aromatic ring represented by is not particularly limited as long as it is an aromatic ring other than a perylene diimide ring, and an aromatic ring having about 1 to 10 rings, preferably about 1 to 8 rings, can be used. Both an aromatic hydrocarbon ring and a heteroaromatic ring can be used (however, R ３ and R ４ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar ２ is an aromatic ring other than a perylene diimide ring which may have a substituent), but a fused aromatic hydrocarbon ring is preferred from the viewpoints of ease of precision synthesis, ease of improving protein transport efficiency, and ease of transporting proteins into cells. Specific examples of such aromatic rings include a benzene ring, a naphthalene ring, an anthracene ring, a phenanthrene ring, a tetracene ring, a pyrene ring, a chrysene ring, a triphenylene ring, a pentacene ring, a perylene ring, a benzopyrene ring, and a coronene ring.

[0088] Ar in general formula (2A) ２ The aromatic ring represented by the formula (I) may have a substituent. The substituent is not particularly limited, and examples thereof include a hydroxyl group, a halogen atom (such as a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom), an alkyl group described below, an alkoxy group (such as a methoxy group, an ethoxy group, or an n-propoxy group), an aryl group described below, and an alkoxycarbonyl group (such as a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, or an n-butyloxycarbonyl group).

[0089] Considering that the protein transport material of the present invention is used to transport proteins, that is, is used in vivo, it is preferable to employ a substituent that can easily improve the solubility in physiological buffers, that is, that can easily improve water solubility. ２Examples of the substituent that the aromatic ring represented by the formula (I) has include, preferably, a hydroxyl group, an alkoxy group (e.g., a methoxy group, an ethoxy group, an n-propoxy group), an alkoxycarbonyl group (e.g., a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an n-butyloxycarbonyl group), etc., more preferably, a hydroxyl group, an alkoxycarbonyl group (e.g., a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an n-butyloxycarbonyl group), etc., and even more preferably, an alkoxycarbonyl group (e.g., a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an n-butyloxycarbonyl group), etc.

[0090] When these substituents are present, the number of the substituents is not particularly limited, but from the viewpoints of facilitating precision synthesis and improving water solubility, the number of the substituents is preferably 1 to 10, more preferably 2 to 8, and even more preferably 3 to 6.

[0091] In the general formula (2B), Ar ３ The nitrogen-containing heterocycle represented by the formula (I) is not particularly limited as long as it is a nitrogen-containing heterocycle, and a heterocycle having about 1 to 10 rings, preferably about 1 to 8 rings, can be used (however, R ３ and R ４ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar ３ represents a nitrogen-containing heterocycle other than a perylene diimide ring which may have a substituent), specific examples thereof include a pyrrole ring, a pyridine ring, an imidazole ring, a pyrazole ring, an oxazole ring, a thiazole ring, a pyridazine ring, a pyrimidine ring, a pyrazine ring, an indole ring, an isoindole ring, a benzimidazole ring, a quinoline ring, an isoquinoline ring, a quinoxaline ring, and a carbazole ring.

[0092] Ar in general formula (2B) ３The nitrogen-containing heterocycle represented by the formula (I) may have a substituent. The substituent is not particularly limited, and examples thereof include a hydroxyl group, a halogen atom (such as a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom), an alkyl group described below, an alkoxy group (such as a methoxy group, an ethoxy group, or an n-propoxy group), an aryl group described below, and an alkoxycarbonyl group (such as a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, or an n-butyloxycarbonyl group).

[0093] Considering that the protein transport material of the present invention is used to transport proteins, that is, is used in vivo, it is preferable to employ a substituent that can easily improve the solubility in physiological buffers, that is, that can easily improve water solubility. ３ Examples of the substituent possessed by the nitrogen-containing heterocycle represented by the formula (I) include preferably a hydroxyl group, an alkoxy group (a methoxy group, an ethoxy group, an n-propoxy group, etc.), an alkoxycarbonyl group (a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an n-butyloxycarbonyl group, etc.), and the like, more preferably a hydroxyl group, an alkoxycarbonyl group (a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an n-butyloxycarbonyl group, etc.), and even more preferably an alkoxycarbonyl group (a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an n-butyloxycarbonyl group, etc.), and the like.

[0094] When these substituents are present, the number of the substituents is not particularly limited, but from the viewpoints of facilitating precision synthesis and improving water solubility, the number of the substituents is preferably 1 to 10, more preferably 2 to 8, and even more preferably 3 to 6.

[0095] In general formula (2A), the divalent group represented by Y is not particularly limited, and examples thereof include divalent groups having 1 to 5, preferably 1 to 4, and more preferably 1 to 3 atoms in the main chain. Examples of atoms constituting the main chain include nitrogen atoms, sulfur atoms, oxygen atoms, and carbon atoms. From the viewpoints of ease of precision synthesis, ease of improving protein transport efficiency, and ease of transporting proteins into cells, nitrogen atoms, oxygen atoms, carbon atoms, and the like are preferred. The divalent group may be substituted, and examples of the substituent include halogen atoms (fluorine atoms, chlorine atoms, iodine atoms, bromine atoms, etc.), oxo groups, and alkyl groups described below.

[0096] Specific examples of Y in the general formula (2A) include a bond, —O—, and —OCH ３ -, -OCH ２ CH ３ -, -OCH ２ CH ２ CH ３ -, -CH ３ O-, -CH ２ CH ３ O-, -CH ２ CH ２ CH ３ O-, -S-, -CH ２ -SO ２ -CH ２ -, -NH-SO ２ -, -SO ２ -NH-, -CO-, -CO-NH-CH ２ -, -NH-CO-CH ２ --etc.

[0097] In general formula (2B), R ４ The hydrocarbon group represented by is not particularly limited, and examples thereof include alkyl groups, aryl groups, and groups formed by any combination thereof (aralkyl groups, alkylaryl groups, alkylaralkyl groups, etc.). Among these, alkyl groups are preferred from the viewpoints of ease of precision synthesis, ease of improving water solubility, ease of improving protein transport efficiency, and ease of transporting proteins into cells.

[0098] R ４The alkyl group as the hydrocarbon group represented by the formula (I) includes any of linear, branched, and cyclic (preferably linear or branched, more preferably linear) alkyl groups. The number of carbon atoms in the alkyl group (in the case of linear or branched) is not particularly limited, and is, for example, preferably 1 to 5, and more preferably 1 to 3. The number of carbon atoms in the alkyl group (in the case of cyclic) is not particularly limited, and is, for example, preferably 3 to 7, and more preferably 4 to 6. Specific examples of the alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a tert-butyl group, a sec-butyl group, a cyclopentyl group, and a cyclohexyl group.

[0099] R ４ The aryl group as the hydrocarbon group represented by the formula (I) is not particularly limited, but preferably has 6 to 12 carbon atoms, and more preferably 6 to 8 carbon atoms. The aryl group may be either monocyclic or polycyclic (e.g., bicyclic, tricyclic, etc.), but is preferably monocyclic. Specific examples of the aryl group include a phenyl group, a naphthyl group, a biphenyl group, a pentalenyl group, an indenyl group, an anthracenyl group, a phenanthrenyl group, a fluorenyl group, a tetracenyl group, a pyrenyl group, a chrysenyl group, a triphenylenyl group, a fluoranthenyl group, a dibenzopentalenyl group, a pentacenyl group, a perylenyl group, a benzopyrenyl group, a coronenyl group, and a corannulenyl group.

[0100] R ４ The aralkyl group as the hydrocarbon group represented by the formula (I) is not particularly limited, and examples thereof include aralkyl groups in which a hydrogen atom (for example, 1 to 3, preferably 1 hydrogen atom) of the linear or branched alkyl group described above is substituted with the aryl group described above. Specific examples of the aralkyl group include a benzyl group and a phenethyl group.

[0101] R ４The alkylaryl group as the hydrocarbon group represented by the formula (I) is not particularly limited, and examples thereof include alkylaryl groups in which the hydrogen atoms (e.g., 1 to 3, preferably 1 hydrogen atom) of the aryl group are substituted with the linear or branched alkyl group described above. Specific examples of such alkylaryl groups include tolyl and xylyl groups.

[0102] R ４ The alkylaralkyl group as the hydrocarbon group represented by the formula (I) is not particularly limited, and examples thereof include alkylaralkyl groups in which a hydrogen atom (e.g., 1 to 3, preferably 1 hydrogen atom) on the aromatic ring of the aralkyl group is substituted with a linear or branched alkyl group as described above.

[0103] R ４ In the case where the hydrocarbon group represented by the formula (I) has a substituent, examples of the substituent that may be possessed include a hydroxyl group, a halogen atom (a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, etc.), the alkyl groups mentioned above, alkoxy groups (a methoxy group, an ethoxy group, an n-propoxy group, etc.), the aryl groups mentioned above, and alkoxycarbonyl groups (a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an n-butyloxycarbonyl group, etc.).

[0104] When these substituents are present, the number of the substituents is not particularly limited, but may be, for example, 1 to 6, preferably 1 to 4, and more preferably 1 or 2.

[0105] Specific examples of the anionic group or cationic group that satisfies the above conditions include:

[0106]

[0107] etc.

[0108] The polycyclic compound represented by general formula (1) constituting the protein transport material of the present invention that satisfies the above-mentioned conditions is, for example,

[0109]

[0110]

[0111]

[0112]

[0113] etc.

[0114] Among the polycyclic compounds represented by the general formula (1) as described above, the polycyclic compounds represented by the general formula (1'):

[0115]

[0116] [In the formula, Ar １ R' represents a fused aromatic ring which may have a substituent. R' represents a group represented by general formula (2A'):

[0117]

[0118] (In the formula, Ar ２ represents an aromatic ring which may have a substituent. Y represents a bond or a divalent group. n represents an integer of 1 or more. When n is an integer of 2 or more, the n Rs may be the same or different. ], preferably a polycyclic aromatic compound represented by the general formula (1A'):

[0119]

[0120] [In the formula, Ar １ represents a fused aromatic ring which may have a substituent. １’ and R ２’ are the same or different and are represented by the general formula (2A'):

[0121]

[0122] (In the formula, Ar ２ represents an aromatic ring which may have a substituent; and Y represents a bond or a divalent group.] represents a group represented by the following formula:

[0123]

[0124] [In the formula, R １ ' and R ２ ' are the same or different and represent a group represented by the general formula (2A'):

[0125]

[0126] (In the formula, Ar ２represents an aromatic ring which may have a substituent; Y represents a bond or a divalent group. ５ , R ６ , R ７ and R ８ are the same or different and represent a hydrogen atom, a hydroxyl group, a halogen atom, an alkyl group, an alkoxy group, an aryl group, or an alkoxycarbonyl group. ５ , R ６ , R ７ and R ８ at least one of which represents a hydroxyl group, an alkoxy group, or an alkoxycarbonyl group.] is a novel compound that has not been described in any literature.

[0127] The method for producing such a polycyclic compound is not particularly limited, and it can be produced by various methods. For example, a compound represented by the general formula (3):

[0128]

[0129] [In the formula, Ar １ and n is the same as above. １ represents a halogen atom, or a boronic acid or ester group thereof. When n is an integer of 2 or more, n X １ may be the same or different.] with a compound represented by general formula (4): R'-Y (4) [wherein R' represents an anionic group or a cationic group which may be protected, and Y represents a halogen atom, or a boronic acid or an ester group thereof.] Here, the anionic group or the cationic group is, as described above, a compound represented by general formula (2A) or (2B):

[0130]

[0131] [In the formula, Ar ２ represents an aromatic ring which may have a substituent. ３ and R ４ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar ２ represents an aromatic ring other than a perylene diimide ring which may have a substituent. ３represents a nitrogen-containing heterocycle which may have a substituent, provided that R ３ and R ４ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar ３ R is a nitrogen-containing heterocycle other than a perylene diimide ring which may have a substituent. ３ represents a carboxy group; a primary, secondary, or tertiary amino group; a nitrogen cation-containing group; a sulfo group; a phosphate group; an ammonium group; a phosphonium group; or a sulfonium group. ４ represents a hydrogen atom or a hydrocarbon group, and Y represents a bond or a divalent group.

[0132] However, X in general formula (3) １ is a halogen atom, Y in the general formula (4) is preferably a boronic acid or ester group thereof, and X in the general formula (3) is preferably a boronic acid or ester group thereof. １ When is a boronic acid or ester group thereof, Y in general formula (4) is preferably a halogen atom.

[0133] In the general formulas (3) and (4), X １ The halogen atom represented by Y includes a chlorine atom, a bromine atom, an iodine atom, and the like.

[0134] In the general formulas (3) and (4), the boronic acid or ester thereof represented by Y is

[0135]

[0136] [Wherein, two R １４ are the same or different and represent a hydrogen atom or an alkyl group. １４ may be taken together to form a ring with the adjacent —O—B—O—. ] is preferred.

[0137] R of the above boronic acid or ester group thereof １４ is a hydrogen atom or an alkyl group.

[0138] The alkyl group can be any of those mentioned above, and the types and numbers of the substituents are also the same.

[0139] Also, R１４ When is an alkyl group, R １４ may combine with the adjacent —O—B—O— to form a ring. In this case, the two oxygen atoms are bonded via an alkylene group (an alkylene group having 1 to 10 carbon atoms, such as a methylene group, an ethylene group, a trimethylene group, or a tetramethylene group).

[0140] Examples of such boronic acid or ester groups include:

[0141]

[0142] [In the above formula, R １５ and R １６ and are the same or different and represent a hydrogen atom or an alkyl group.

[0143] The above R １５ and R １６ is a hydrogen atom or an alkyl group.

[0144] The alkyl group can be any of those mentioned above, and the types and numbers of the substituents are also the same.

[0145] The boronic acid or ester group thereof may have a substituent. When the boronic acid or ester group thereof is substituted, examples of the substituent include a halogen atom (a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, etc.), an alkoxy group (a methoxy group, an ethoxy group, an n-propoxy group, etc.), the above-mentioned aryl group, the above-mentioned boronic acid or ester group thereof, a cyano group, etc. When the boronic acid or ester group thereof has these substituents, the number of the substituents may be, for example, 1 to 5.

[0146] Examples of such compounds represented by general formula (3) include:

[0147]

[0148] etc.

[0149] In the general formula (4), R' is an anionic group or a cationic group, and the anionic group or cationic group may be protected.

[0150] When an anionic group or a cationic group is protected, the protecting group is not particularly limited, and examples thereof include an alkoxycarbonyl group, an acyl group, an alkylsulfonyl group, an arylsulfonyl group, and the like. These protecting groups may have a substituent such as the above-mentioned alkyl group, aryl group, aralkyl group, alkylaryl group, or alkylaralkyl group. Among these, an alkoxycarbonyl group is preferred as the protecting group for an anionic group or a cationic group from the viewpoint of ease of synthesis, yield, and the like. Specific examples thereof include a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an isopropoxycarbonyl group, and a tert-butyloxycarbonyl group. When a protecting group for an anionic group or a cationic group is employed, it is preferable to deprotect it by a conventional method after the reaction.

[0151] Examples of such compounds represented by general formula (4) include:

[0152]

[0153]

[0154] [wherein Boc represents a tert-butyloxycarbonyl group] and the like.

[0155] The reaction is not particularly limited, but can be carried out by Suzuki-Miyaura coupling, and the reaction conditions can be those usually used in Suzuki-Miyaura coupling.

[0156] In addition, when R′ is a protecting group for an anionic or cationic group, the polycyclic aromatic compound used in the protein transport material of the present invention can be obtained by deprotecting it using a conventional method after the above reaction.

[0157] (1-2) Polycyclic aromatic compound (general formula (5)) In the present invention, in addition to the polycyclic compound represented by the general formula (1), a polycyclic aromatic compound represented by the general formula (5):

[0158]

[0159] [In the formula, R １７ and R １８and each may be the same or different and represent an aryl group which may have a substituent.] A polycyclic compound having one or more structures represented by the following formula in its main skeleton can also be used as a protein transport material, similar to the polycyclic compound represented by the above general formula (1).

[0160] As polycyclic compounds having one or more structures represented by general formula (5) in the main skeleton, from the viewpoints of ease of precision synthesis, ease of improving protein transport efficiency, and ease of transporting proteins into cells, general formulas (5A) and (5B):

[0161]

[0162] [In the formula, Ar ４ represents a fused ring derived from an optionally substituted fused aromatic ring. １７ , R １８ , R １７ａ , R １８ａ , R １７ｂ and R １８ｂ and may be the same or different and represent an aryl group which may have a substituent.] are preferred.

[0163] Ar ４ a fused aromatic ring in a fused ring derived from a fused aromatic ring represented by １７ , R １８ , R １７ａ , R １８ａ , R １７ｂ and R １８ｂ The aryl group represented by the formula (I) can be any of those mentioned above. The same applies to the substituent. However, from the viewpoints of the conversion rate of the reaction, the selectivity of the target product, the yield, etc., it is preferable to have a bulky group as the substituent. From such a viewpoint, it is preferable to have a branched or cyclic alkyl group, an aryl group, etc. as the substituent.

[0164] In addition, Ar ４ In the above formula, when the ring adjacent to the triazole ring is a six-membered ring, it is often a 1,3-cyclohexadiene ring. ４ In the above formula, the fused ring derived from the fused aromatic ring may mean a fused ring that has become a 1,3-cyclohexadiene ring when the ring adjacent to the triazole ring among the fused aromatic rings is a 6-membered ring.

[0165] Among the polycyclic compounds having one or more structures represented by such general formula (5) in the main skeleton, those having general formula (5'):

[0166]

[0167] [In the formula, R １７ and R １８ R may be the same or different and represent an aryl group which may have a substituent. １９ , R ２０ , R ２１ and R ２２ are the same or different and represent a hydrogen atom, an alkyl group which may have a substituent, or an aryl group which may have a substituent. １９ and R ２０ , R ２０ and R ２１ , and R ２１ and R ２２ are taken together at least one position to form an aromatic ring, and may be taken together at other positions to form a ring.] in the main skeleton is a novel compound not described in any literature.

[0168] In general formula (5′), R １７ and R １８ The aryl group represented by the formula (I) can be any of those mentioned above. The types and numbers of the substituents are also the same.

[0169] In general formula (5′), R １９ , R ２０ , R ２１ and R ２２ The alkyl group and aryl group represented by the formula (I) can be those described above. The same applies to the type and number of the substituents.

[0170] In addition, R １９ and R ２０ , R ２０ and R ２１ , and R ２１ and R ２２are joined together at least at one position to form an aromatic ring, and may be joined together at other positions to form a ring. In this case, the aromatic ring may be any of those described above, and in addition to the aromatic rings described above, a cyclohexadiene ring, a cyclohexane ring, or the like may also be used as the ring.

[0171] The polycyclic compound having one or more structures represented by the general formula (5) in the main skeleton can be, for example, a compound obtained by combining a polycyclic aromatic compound and a compound represented by the general formula (6):

[0172]

[0173] [In the formula, R １７ and R １８ is the R １７ａ , R １８ａ , R １７ｂ and R １８ｂ and the groups may be the same or different and each represents an aryl group which may have a substituent.]

[0174] The polycyclic aromatic compound used is selected from the group consisting of a polycyclic aromatic compound which is easily cyclized to form a structure represented by general formula (5) by reaction with the compound represented by general formula (6), and a polycyclic aromatic compound which is easily cyclized to form a structure represented by general formula (5).

[0175]

[0176] It is preferable that the compound has a structure represented by the following formula:

[0177] The polycyclic aromatic compound that can be used is not particularly limited, but examples thereof include naphthalene, indene, anthracene, phenanthrene, tetracene, pyrene, chrysene, triphenylene, fluoranthene, dibenzopentalene, pentacene, perylene, benzopyrene, coronene, and corannulene.

[0178] Examples of the compound represented by general formula (6) include:

[0179]

[0180] etc.

[0181] The amount of the compound represented by general formula (6) used is not particularly limited and varies depending on the polycyclic aromatic compound used as a substrate. However, from the viewpoints of the conversion rate of the reaction, the selectivity for the target product, the yield, etc., the amount is preferably 1 to 30 moles, and more preferably 1.1 to 20 moles, per mole of the polycyclic aromatic compound.

[0182] The reaction can also be carried out in the presence of a hypohalous acid compound. Specific examples of the hypohalous acid compound include hypochlorous acid compounds such as methyl hypochlorite, ethyl hypochlorite, and tert-butyl hypochlorite; and hypobromous acid compounds such as methyl hypobromite, ethyl hypobromite, and tert-butyl hypobromite. These hypohalous acid compounds can be used alone or in combination of two or more.

[0183] The amount of the hypohalous acid compound used is not particularly limited and varies depending on the polycyclic aromatic compound used as a substrate. However, from the viewpoints of the conversion rate of the reaction, the selectivity for the target product, the yield, etc., the amount of the hypohalous acid compound used is preferably 1 to 30 mol, and more preferably 1.1 to 20 mol, per 1 mol of the polycyclic aromatic compound.

[0184] The reaction can also be carried out in the presence of a hexafluorophosphate compound. Specific examples of the hexafluorophosphate compound include potassium hexafluorophosphate and sodium hexafluorophosphate. These hexafluorophosphate compounds can be used alone or in combination of two or more.

[0185] The amount of the hexafluorophosphate compound used is not particularly limited and varies depending on the polycyclic aromatic compound used as a substrate. However, from the viewpoints of the conversion rate of the reaction, the selectivity for the target product, the yield, and the like, the amount is preferably 1 to 30 moles, and more preferably 1.1 to 20 moles, per mole of the polycyclic aromatic compound.

[0186] The reaction can also be carried out in the presence of a fluorine-containing alcohol. Specific examples of the fluorine-containing alcohol include 2,2,3,3-tetrafluoro-1-propanol, 2,2,2-trifluoroethanol, 1,1,1,3,3,3-hexafluoro-2-propanol, and 2,2,3,3,3-pentafluoro-1-propanol. These fluorine-containing alcohols can be used alone or in combination of two or more.

[0187] The amount of the fluorine-containing alcohol to be used is not particularly limited and varies depending on the polycyclic aromatic compound to be used as a substrate. From the viewpoints of the conversion rate of the reaction, the selectivity for the target product, the yield, etc., the amount of the fluorine-containing alcohol to be used is preferably 1 to 30 mol, more preferably 1.1 to 20 mol, per mol of the polycyclic aromatic compound.

[0188] The reaction is usually carried out in the presence of a solvent. Usable solvents are not particularly limited, but examples thereof include amide compounds such as N,N-dimethylformamide; ether compounds such as tetrahydrofuran; halogenated aliphatic hydrocarbon compounds such as chloroform and dichloromethane; aromatic hydrocarbon compounds such as toluene and xylene; nitrile compounds such as acetonitrile; and ketone compounds such as acetone. These solvents can be used alone or in combination of two or more.

[0189] The reaction atmosphere may be an inert atmosphere such as a nitrogen gas atmosphere or an argon gas atmosphere.

[0190] The reaction temperature is not particularly limited, but can usually be gradually increased from −100 to −50° C. to 10 to 30° C. from the viewpoint of the conversion rate of the reaction, the yield of the target product, selectivity, etc. The reaction time can be set to a time that allows the reaction to be sufficiently completed.

[0191] After completion of the reaction, the product may be purified by a conventional method, if necessary. For example, the crude product may be filtered, and the filtrate may be distilled off under reduced pressure, followed by purification by trituration, to obtain a polycyclic aromatic compound having one or two structures represented by general formula (5) in the main skeleton.

[0192] (1-3) Protein Transport Material In the present invention, the above-described polycyclic compound can be used as it is as the protein transport material of the present invention, that is, it can be used in a minimum essential medium (MEM), or a solvent can be further contained in the protein transport material of the present invention.

[0193] When the protein transport material of the present invention contains a solvent, the solvent is preferably a physiological buffer solution from the viewpoints of protein transport efficiency and safety, taking into consideration that the protein transport material of the present invention will be used in the body.

[0194] When a physiological buffer solution is used as the solvent, the pH is preferably 6.0 to 8.0, more preferably 6.5 to 7.8, and even more preferably 7.0 to 7.6, from the viewpoints of protein transport efficiency and safety.

[0195] Specific examples of such physiological buffer solutions include Tris-buffered saline (TBS), HEPES-buffered saline (HBS), MES-buffered saline (MBS), phosphate buffer, etc. Among these, from the viewpoint of protein transport efficiency, Tris-buffered saline (TBS), HEPES-buffered saline (HBS), MES-buffered saline (MBS), etc. are preferred, Tris-buffered saline (TBS), HEPES-buffered saline (HBS), etc. are more preferred, and HEPES-buffered saline (HBS) is particularly preferred.

[0196] When a solvent is contained in the protein transport material of the present invention, the concentration of the polycyclic compound in the protein transport material of the present invention is not particularly limited, and from the viewpoints of protein transport efficiency and safety, the concentration is preferably 0.01 to 70 μM, more preferably 0.02 to 50 μM, even more preferably 0.05 to 30 μM, and particularly preferably 0.1 to 20 μM.

[0197] Furthermore, the protein transport material of the present invention can also contain additives that have traditionally been contained in protein transport materials, such as antibiotics, antifungals, serum, etc., to the extent that the effects of the present invention are not impaired.

[0198] 2. Uses The protein transport material of the present invention uses small molecules that can be precisely synthesized, and yet has excellent protein transport efficiency and is capable of efficiently transporting proteins into cells. In other words, the protein transport material of the present invention can be mixed with a protein, administered to a living body, delivered to a target tissue, and then used to transport the protein to target tissue cells. Therefore, the present invention also includes pharmaceutical compositions (protein pharmaceutical compositions) in which the protein transport material of the present invention contains a protein.

[0199] There are no particular limitations on the proteins that can be transported, and a wide variety of proteins can be used.

[0200] For example, when R in general formula (1) has an anionic group, the protein transport material of the present invention can have a negative charge and can therefore suitably transport cationic proteins. The cationic protein may be one whose charge has been artificially converted so that it has more positive charges than negative charges in an aqueous medium at physiological pH. Examples of such cationic proteins include trypsin, cytochrome c, saporin, and lysozyme.

[0201] Furthermore, when general formula (1) contains a cationic group as R or when the main skeleton contains one or two structures represented by general formula (5), the protein transport material of the present invention can have a positive charge and can therefore suitably transport anionic proteins. The anionic protein may be one whose charge has been artificially converted so that it has more negative charges than positive charges in an aqueous medium at physiological pH. Examples of such anionic proteins include R-phycoerythrin, albumin, β-galactosidase, and green fluorescent protein (GFP).

[0202] The protein transport material of the present invention can be used as a pharmaceutical composition (protein pharmaceutical composition) by mixing it with a protein to form a complex. When preparing a pharmaceutical composition, the protein can form a complex with the polycyclic compound through electrostatic interaction. Therefore, the amount of protein is not particularly limited, but can be determined according to conventional methods.

[0203] The pharmaceutical composition (protein pharmaceutical composition) of the present invention can be used to deliver a protein to a target cell or tissue in vitro or in vivo. The pharmaceutical composition (protein pharmaceutical composition) of the present invention enables the protein to be easily delivered into a target cell in a stabilized state.

[0204] To deliver a protein to a target cell or tissue using the pharmaceutical composition (protein pharmaceutical composition) of the present invention, the pharmaceutical composition (protein pharmaceutical composition) can be brought into a state where it can come into contact with the target cell or tissue.

[0205] To achieve contact between the pharmaceutical composition (protein pharmaceutical composition) of the present invention and target cells or tissues in vitro, the target cells or tissues can be cultured in the presence of the pharmaceutical composition (protein pharmaceutical composition) of the present invention, or the pharmaceutical composition (protein pharmaceutical composition) of the present invention can be added to a culture of the target cells or tissues.

[0206] To achieve in vivo contact between the pharmaceutical composition (protein pharmaceutical composition) of the present invention and target cells or tissues, the pharmaceutical composition (protein pharmaceutical composition) of the present invention can be administered to an individual requiring introduction of the protein (or an individual to be treated) by an administration method commonly used in the art, such as gene therapy. Examples of such individuals include, but are not limited to, mammals (mammalian cells) such as humans, mice, rats, rabbits, dogs, cats, monkeys, cows, horses, and pigs; plants (plant cells) such as rice, corn, wheat, potato, sugarcane, and soybean; insects (insect cells); and Escherichia coli. Examples of administration methods include direct introduction or transplantation near or into target cells or tissues, intravenous injection, arterial injection, intramuscular injection, oral administration, and pulmonary administration. Conditions such as the dosage, number of administrations, and administration period can be appropriately determined depending on the type and condition of the subject animal.

[0207] Diseases that can be treated with the pharmaceutical composition (protein pharmaceutical composition) of the present invention are not particularly limited as long as they are caused by inappropriate functional expression of genes, and examples include cancers (lung cancer, pancreatic cancer, brain tumors, liver cancer, breast cancer, colon cancer, neuroblastoma, bladder cancer, etc.), cardiovascular diseases, musculoskeletal diseases, and central nervous system diseases.

[0208] The pharmaceutical composition of the present invention may contain other additives commonly used in pharmaceutical preparations. Examples of other additives include excipients, bulking agents, fillers, binders, wetting agents, disintegrants, lubricants, surfactants, dispersants, buffers, preservatives, solubilizers, antiseptics, flavoring agents, soothing agents, stabilizers, and isotonicity agents. Such additives may be used alone or in any combination and ratio of two or more. Details such as the type and amount of these other components can be appropriately determined by those skilled in the art depending on the purpose, use, and method of use of the pharmaceutical composition.

[0209] The pharmaceutical composition of the present invention may take any form, but is usually used as an intravenous injection (including drip infusion), and is provided, for example, in the form of a unit dose ampoule or other dosage container.

[0210] The pharmaceutical composition of the present invention can be used in any manner, and the pharmaceutical composition containing the protein transport material of the present invention can be administered as is.

[0211] Although the present invention has been described in detail above, the present invention is not limited to the above-described configurations and various modifications are possible. For example, the present invention also includes the following configurations. Note that the above-described explanations can be applied to each term in the following configurations, and the same applies to preferred embodiments.

[0212] Item 1. A protein transport material containing a polycyclic aromatic compound, wherein the polycyclic aromatic compound is represented by general formula (1):

[0213]

[0214] [In the formula, Ar １ represents a fused aromatic ring which may have a substituent, provided that when R is a group having a primary, secondary or tertiary amino group; or a group having a nitrogen cation-containing group, Ar １ is a fused aromatic ring other than a perylene diimide ring which may have a substituent. R represents an anionic group or a cationic group. n represents an integer of 1 or more. When n is an integer of 2 or more, the n Rs may be the same or different.] or is represented by general formula (5):

[0215]

[0216] [In the formula, R １７ and R １８ and each of the groups may be the same or different and represent an aryl group which may have a substituent.] A protein transport material having one or two structures represented by the following formula in its main skeleton.

[0217] Item 2. The polycyclic aromatic compound represented by the general formula (1) is represented by the general formula (1A):

[0218]

[0219] [In the formula, Ar １ represents a fused aromatic ring which may have a substituent. １ and R ２ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar１ R is a fused aromatic ring other than a perylene diimide ring which may have a substituent. １ and R ２ and are the same or different and represent an anionic group or a cationic group.

[0220] Item 3. Said Ar １ Item 3. The protein transport material according to Item 1 or 2, wherein is a fused aromatic hydrocarbon ring.

[0221] Item 4. The protein transport material according to any one of Items 1 to 3, wherein the anionic group or cationic group is a group having a carboxy group, a group having a primary, secondary, or tertiary amino group, a group having a nitrogen cation-containing group, a group having a sulfo group, a group having a phosphate group, a group having an ammonium group, a group having a phosphonium group, or a group having a sulfonium group.

[0222] Item 5. The anionic group or cationic group is represented by general formula (2A) or (2B):

[0223]

[0224] [In the formula, Ar ２ represents an aromatic ring which may have a substituent. ３ and R ４ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar ２ represents an aromatic ring other than a perylene diimide ring which may have a substituent. ３ represents a nitrogen-containing heterocycle which may have a substituent, provided that R ３ and R ４ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar ３ R is a nitrogen-containing heterocycle other than a perylene diimide ring which may have a substituent. ３ represents a carboxy group; a primary, secondary, or tertiary amino group; a nitrogen cation-containing group; a sulfo group; a phosphate group; an ammonium group; a phosphonium group; or a sulfonium group. ４represents a hydrogen atom or a hydrocarbon group; and Y represents a bond or a divalent group. Item 5. The protein transport material according to Item 4, wherein

[0225] Item 6. Said R ３ is a carboxy group, a primary amino group, an imidazolium group which may have a substituent, a pyridinium group which may have a substituent, a tetraalkylammonium group which may have a substituent, or a triazolium group which may have a substituent.

[0226] Item 7. Ar in the general formula (1) １ Item 7. The protein transport material according to any one of Items 1 to 6, wherein the number of fused aromatic rings as the ring unit is 2 to 10.

[0227] Item 8. The polycyclic aromatic compound having one or two structures represented by the general formula (5) in the main skeleton is represented by general formula (5A) or (5B):

[0228]

[0229] [In the formula, Ar ４ represents a fused aromatic ring which may have a substituent. １７ , R １８ , R １７ａ , R １８ａ , R １７ｂ and R １８ｂ and each of the groups may be the same or different and represent an aryl group which may have a substituent.

[0230] Item 9. Said Ar ４ Item 9. The protein transport material according to Item 8, wherein is a fused aromatic hydrocarbon ring.

[0231] Item 10. Ar in the general formulas (5A) and (5B) ４ Item 10. The protein transport material according to Item 8 or 9, wherein the number of fused aromatic rings as the ring unit is 2 to 10.

[0232] Item 11. The protein transport material according to any one of Items 1 to 10, further comprising a physiological buffer solution having a pH of 6.0 to 8.0.

[0233] Item 12. The protein transport material according to any one of Items 1 to 11, which is a protein transport material for transporting protein to at least one cell selected from the group consisting of mammalian cells, plant cells, insect cells, and Escherichia coli.

[0234] Item 13. A pharmaceutical composition comprising the protein transport material according to any one of Items 1 to 12 and a protein.

[0235] Item 14. A genome editing composition comprising the protein transport material according to any one of Items 1 to 12 and a protein.

[0236] Item 15. General formula (1'):

[0237]

[0238] [In the formula, Ar １ represents a fused aromatic ring which may have a substituent; R represents a group having a carboxy group; n represents an integer of 1 or more; when n is an integer of 2 or more, the n Rs may be the same or different.] or is represented by general formula (5):

[0239]

[0240] [In the formula, R １７ and R １８ and each of the groups may be the same or different and represent an aryl group which may have a substituent.] A polycyclic aromatic compound having one or two structures represented by the following formula in its main skeleton.

[0241] Item 16. The polycyclic aromatic compound represented by the general formula (1) is represented by the general formula (1A'):

[0242]

[0243] [In the formula, Ar １ represents a fused aromatic ring which may have a substituent. １’ and R ２’ and each may be the same or different and represent a group having a carboxy group.

[0244] Item 17. The polycyclic aromatic compound represented by the general formula (1) is a compound represented by the general formula (1A1′):

[0245]

[0246] [In the formula, R １ and R ２ are the same or different and represent a group having a carboxy group. ５ , R ６ , R ７ and R ８ are the same or different and represent a hydrogen atom, a hydroxyl group, a halogen atom, an alkyl group, an alkoxy group, an aryl group, or an alkoxycarbonyl group. ５ , R ６ , R ７ and R ８ Item 17. The polycyclic aromatic compound according to item 15 or 16, wherein at least one of the groups represents a hydroxyl group, an alkoxy group, or an alkoxycarbonyl group.

[0247] Item 18. The polycyclic aromatic compound having one or two structures represented by the general formula (5) in the main skeleton is represented by general formula (5A) or (5B):

[0248]

[0249] [In the formula, Ar ４ represents a fused aromatic ring which may have a substituent. １７ , R １８ , R １７ａ , R １８ａ , R １７ｂ and R １８ｂ and each of the groups may be the same or different and represent an aryl group which may have a substituent.

[0250] The present invention will be specifically explained below by way of examples, but the present invention is not limited to these examples.

[0251] Synthesis Example 1: Synthesis of KTU207

[0252]

[0253] Compound 21 (502 mg, 1.14 mmol), bispinacolatodiboron (B2pin2) (398 mg, 1.66 mmol), [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride·dichloromethane adduct (Pd(dppf)Cl2·CHCl2) (132 mg, 162 μmol), and potassium acetate (KOAc) (329 mg, 3.35 mmol) were dissolved in 1,4-dioxane (15 mL). The mixture was stirred at 100°C under a nitrogen atmosphere for 15 hours. The resulting solid was then removed by filtration, water was added, and the mixture was extracted three times with ethyl acetate (20 mL). The resulting organic layer was washed with saturated brine, dried over Na2SO4, and evaporated under reduced pressure to give the crude product. The crude product was purified by column chromatography to give compound 22 (342 mg, 59%). 1 H NMR (600 MHz, CDCl3) δ 7.71 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 9.0 Hz, 2H), 3.60-3.55 (m, 4H), 3.25-3.18 (s, 4H), 1.48 (s, 9H), 1.32 (s, 12H).

[0254] Compound 1 (102 mg, 125 μmol) (J. Org. Chem. 2014, 79, 6655.), compound 22 (110 mg, 284 μmol), tetrakis(triphenylphosphine)palladium (Pd(PPh3)4) (15.0 mg, 13.0 μmol), and Na2CO3 (112 mg, 1.05 mmol) were dissolved in toluene (1.2 mL), water (0.6 mL), and ethanol (0.3 mL). The mixture was stirred at 80 °C under a nitrogen atmosphere for 18 h. The resulting solid was then filtered off and extracted three times with dichloromethane (20 mL). The resulting organic layer was washed with saturated brine, dried over Na2SO4, and evaporated under reduced pressure to give the crude product. The crude product was purified by preparative thin-layer chromatography to give compound 23 (144 mg, 98%). 1H NMR (600 MHz, CDCl3) δ 8.02 (s, 2H), 7.64 (d, J = 7.8 Hz, 2H), 7.56 (d, J = 7.8 Hz, 2H), 7. 39 (d, J = 8.4 Hz, 4H), 6.95 (d, J = 8.4 Hz, 4H), 4.31 (t, J = 6.6 Hz, 4H), 4.28 (t, J = 6.6 Hz, 4H),3.65-3.60 (m, 8H), 3.24 (br, 8H), 1.78-1.71 (m, 8H), 1.50-1.43 (m, 26H), 0.99-0.95 (m, 12H); MS (MALDI-TOF MS) m / z calculation for C 70 H 84 N4O 12 [M] + : 1172.61, found : 1172.62.

[0255] Compound 23 (13.0 mg, 10.5 μmol) was dissolved in 1.0 mL of dichloromethane. 0.5 mL of trifluoroacetic acid (TFA) was added and the mixture was stirred at 19 °C for 2 hours. 6 mL of 1 M aqueous sodium hydroxide was then added, and the mixture was extracted three times with dichloromethane (10 mL). The resulting organic layer was washed with saturated brine, dried over Na2SO4, and evaporated under reduced pressure to give KTU207 (9.1 mg, 91%). 1 H NMR (600 MHz, CD2Cl2) δ 8.02 (s, 2H), 7.69 (d, J = 7.8 Hz, 2H), 7.55 (d, J = 7.8 Hz, 2H), 7.39 (d, J = 9.0 Hz, 4H), 6.96 (d, J = 8.4 Hz, 4H), 4.28 (t, J = 7.2 Hz, 4H), 4.24 (t, J = 6.6 Hz, 4H), 3.22-3.18 (m, 8H), 3.04-2.98 (m, 8H), 1.77-1.70 (m, 8H), 1.48-1.43 (m, 8H), 0.98-0.95 (m, 12H).

[0256] Synthesis Example 2: Synthesis of KTU059

[0257]

[0258] Compound 1 (206 mg, 254 μmol) (J. Org. Chem. 2014, 79, 6655.), compound 2 (228 mg, 628 μmol) (J. Am. Chem. Soc. 2014, 136, 6505.), tetrakis(triphenylphosphine)palladium (Pd(PPh3)4) (29.9 mg, 25.9 μmol), and Na2CO3 (192 mg, 1.81 mmol) were dissolved in toluene (3.0 mL), water (1.0 mL), and ethanol (0.5 mL). The mixture was stirred at 80 °C under a nitrogen atmosphere for 13 hours. The resulting solid was then filtered off and extracted three times with dichloromethane (20 mL). The resulting organic layer was washed with saturated brine, dried over Na2SO4, and evaporated under reduced pressure to give the crude product. The resulting crude product was purified by preparative thin layer chromatography to give Compound 3 (135 mg, 47%). 1 H NMR (600 MHz, CD2Cl2) δ 8.01 (s, 2H), 7.61 (d, J = 7.8 Hz, 2H), 7.56 (d, J = 7.8 Hz, 2H), 7.44 (d, J = 8.4 Hz, 4H), 6.98 (d, J = 9.0 Hz, 4H), 5.06 (br, 2H), 4.28 (t, 6.6 Hz, 4H), 4.24 (t, 6.6 Hz, 4H), 4.08 (t, J= 4.8 Hz, 4H), 3.55 (d, J = 4.8 Hz, 4H), 1.77-1.70 (m, 8H), 1.49-1.41 (m, 26H), 0.98-0.95 (m, 12H); MS (MALDI-TOF MS) m / z calc. for C 66 H 78 N2O 14 [M] + : 1122.5448, found : 1122.5446.

[0259] Compound 3 (3.4 mg, 5.7 μmol) was dissolved in 0.9 mL of dichloromethane. 0.1 mL of trifluoroacetic acid (TFA) was added and the mixture was stirred at 24 °C for 24 hours. 6 mL of 1 M aqueous sodium hydroxide was then added, and the mixture was extracted three times with dichloromethane (10 mL). The resulting organic layer was washed with saturated brine, dried over Na2SO4, and evaporated under reduced pressure to give KTU059 (15.1 mg, 90%). 1 H NMR (600 MHz, CDCl3) δ 8.02 (s, 2H), 7.58 (d, J = 7.8 Hz, 2H), 7.57 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 9.0 Hz, 4H), 6.96 (d, J = 8. 4 Hz, 4H), 4.32 (t, 7.2 Hz, 4H), 4.28 (t, 7.2 Hz, 4H), 4.07 (t, J = 4.8 Hz, 4H), 3.15 (t, J = 4.8 Hz, 4H), 1.75 (m, 8H), 1.49-1.42 (m, 8H), 0.99-0.96 (m, 12H); MS (MALDI-TOF MS) m / z calc. for C 56 H 62 N2O 10 [M] + : 922.4399, found : 922.4399.

[0260] Synthesis Example 3: Synthesis of KTU205

[0261]

[0262] Compound 27 (50.9 mg, 57.8 μmol) (J. Am. Chem. Soc. 2012, 134, 15169.), compound 21 (292 mg, 857 μmol), tris(dibenzylideneacetone)dipalladium·chloroform adduct (Pd2dba3·CHCl3) (12.2 mg, 11.8 μmol), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (SPhos) (12.5 mg, 30.5 μmol), and Cs2CO3 (243 mg, 744 mmol) were dissolved in toluene (1.5 mL) and water (0.8 mL). The mixture was stirred at 80°C under a nitrogen atmosphere for 17 hours. The mixture was then extracted three times with dichloromethane (10 mL). The resulting organic layer was washed with saturated brine, dried over NaSO, and evaporated under reduced pressure to give the crude product, which was purified by recrystallization and preparative thin-layer chromatography to give Compound 28 (41.3 mg, 46%). 1 H NMR (600 MHz, CDCl3) δ 7.85 (s, 5H), 7.65 (d, J = 8.6 Hz, 10H), 7.04 (d, J = 8.9 Hz, 10H), 3.64 (t, J = 5.0 Hz, 20H), 3.25 (s, 20H), 1.51 (s, 45H).

[0263] Compound 28 (21.4 mg, 13.8 μmol) was dissolved in 1.0 mL of dichloromethane. 1.0 mL of trifluoroacetic acid (TFA) was added, and the mixture was stirred at 19°C for 11 hours. Then, 4 M hydrochloric acid (1,4-dioxane solution) was added, and the mixture was evaporated under reduced pressure. This procedure was repeated three times to obtain KTU205 (17.2 mg, 100%). 1 H NMR (600 MHz, CF3COOD) δ 7.88 (d, J = 7.6 Hz, 10H), 7.78-7.72 (m, 15H), 4.32 (brs, 20H), 4.13 (brs, 20H).

[0264] Synthesis Example 4: Synthesis of SMZ034

[0265]

[0266] Compound 1 (20.0 mg, 25 μmol), compound 4 (38 mg, 126 μmol), tetrakis(triphenylphosphine)palladium (Pd(PPh3)4) (4.0 mg, 3.0 μmol), and Na2CO3 (14 mg, 127 μmol) were dissolved in toluene (100 μL), water (50 μL), and ethanol (25 μL). The mixture was stirred at 90 °C under a nitrogen atmosphere for 18 h. The resulting solid was then filtered off and extracted three times with dichloromethane (20 mL). The resulting organic layer was dried over Na2SO4 and evaporated under reduced pressure to give the crude product. The crude product was purified by preparative thin-layer chromatography to give compound 5 (20 mg, 81%). 1 H NMR (400 MHz, CDCl3) δ 8.06 (d, J = 8.6 Hz, 4H), 8.03 (s, 2H), 7.58 (d, J = 7.9 Hz, 2H), 7.55 (d, J = 8.6 Hz, 4H), 7.48 (d, J = 7.9 Hz, 2H), 4.35-4.26 (m, 8H), 1.81-1.71 (m, 8H), 1.65 (s, 18H), 1.51-1.40 (m, 8H), 1.00-0.94 (m, 12H).

[0267] Compound 5 (10.0 mg, 10 μmol) was dissolved in 0.9 mL of dichloromethane. 0.1 mL of trifluoroacetic acid (TFA) was added and the mixture was stirred at 24 °C for 24 hours. Water was added and the mixture was extracted three times with dichloromethane (20 mL). The resulting organic layer was dried over NaSO and evaporated under reduced pressure to give the crude product. The crude product was purified by washing with hexane to give SMZ034 (8.0 mg, 81%). 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 8.3 Hz, 4H), 8.07 (s, 2H), 7.64 (d, J = 8.3 Hz, 4H), 7.61 (d, J = 8.1 Hz, 2H), 7.49 (d, J = 7.9 Hz, 2H), 4.36-4.29 (m, 8H), 1.82-1.73 (m, 8H), 1.52-1.42 (m, 8H), 1.02-0.94 (m, 12H).

[0268] Synthesis Example 5: Synthesis of SMZ040

[0269]

[0270] Compound 6 (160 mg, 0.7 mmol), di-tert-butyl dicarbonate (BocO) (335 mg, 1.5 mmol), and MgCl (14 mg, 0.15 mmol) were dissolved in tert-butyl alcohol (t-BuOH) (1.5 mL). The mixture was stirred at 40°C under a nitrogen atmosphere for 20 hours. Water was added, and the mixture was extracted three times with ethyl acetate (20 mL). The resulting organic layer was dried over NaSO and evaporated under reduced pressure to give the crude product. The crude product was purified by size exclusion chromatography to give compound 7 (110 mg, 55%). 1 H NMR (400 MHz, CDCl3)δ 7.39 (d, J = 8.4 Hz, 2H), 7.07 (d, J = 8.6 Hz, 2H), 2.85 (t, J = 7.7 Hz, 2H), 2.51 (t, J = 7.7 Hz, 2H), 1.41 (s, 9H).

[0271] Compound 7 (110 mg, 0.4 mmol), potassium acetate (79 mg, 0.8 mmol), bis(pinacolato)diboron (B2pin2) (125 mg, 0.5 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride·dichloromethane adduct (Pd(dppf)Cl2·CHCl2) (25.0 mg, 31 μmol) were dissolved in 1,4-dioxane (2.0 mL). The mixture was stirred at 110°C under a nitrogen atmosphere for 40 hours. The resulting solid was removed by filtration, water was added, and the mixture was extracted three times with ethyl acetate (20 mL). The resulting organic layer was dried over Na2SO4 and evaporated under reduced pressure to give the crude product. The crude product was purified by size exclusion chromatography to give compound 8 (89.0 mg, 69%). 1 H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 7.9 Hz, 2H), 7.21 (d, J = 7.9 Hz, 2H), 2.92 (t, J = 7.8 Hz, 2H), 2.53 (t, J = 7.9 Hz, 2H), 1.42 (s, 9H), 1.33 (s, 12H).

[0272] Compound 1 (19.0 mg, 24 μmol), compound 8 (48.0 mg, 144 μmol), tetrakis(triphenylphosphine)palladium (Pd(PPh3)4) (5 mg, 4 μmol), and Na2CO3 (18 mg, 170 μmol) were dissolved in toluene (0.2 mL), water (100 μL), and ethanol (50 μL). The mixture was stirred at 90 °C under a nitrogen atmosphere for 18 hours. The resulting solid was then removed by filtration and extracted three times with dichloromethane (20 mL). The resulting organic layer was dried over Na2SO4 and evaporated under reduced pressure to give the crude product. The crude product was purified by preparative thin-layer chromatography to give compound 9. 1H NMR (400 MHz, CDCl3) δ 8.03 (s, 2H), 7.54 (s, 4H), 7.41 (d, J = 8.2 Hz, 4H), 7.27-7.25 (m, 4H), 4.33-4.25 (m, 8H), 2.98 (t, J = 7.7 Hz, 4H), 2.62 (t, J = 7.7 Hz, 4H), 1.81-1.70 (m, 8H), 1.50-1.39 (m, 26H), 0.99-0.94 (m, 12H).

[0273] Compound 9 was dissolved in 0.9 mL of dichloromethane. 0.1 mL of trifluoroacetic acid (TFA) was added and the mixture was stirred at 24 °C for 24 hours. Water was added and the mixture was extracted three times with dichloromethane (20 mL). The resulting organic layer was dried over Na2SO4 and evaporated under reduced pressure to obtain the crude product. The crude product was purified by washing with hexane to obtain SMZ040 (22.0 mg, 93% yield for two steps). 1 H NMR (400 MHz, CDCl3) δ 8.03 (s, 2H), 7.54 (d, J = 8.2 Hz, 2H), 7.51 (d, J = 7.9 Hz, 2H), 7.42 (d, J = 8.2 Hz, 4H), 7.28 (d, J = 8.4 Hz, 4H), 4.36-4.26 (m, 8H), 3.04 (t, J = 7.6 Hz, 4H), 2.77 (t, J = 7.6 Hz, 4H), 1.80-1.68 (m, 8H), 1.52-1.39 (m, 8H), 1.04-0.92 (m, 12H).

[0274] Synthesis Example 6: Synthesis of RKO021

[0275]

[0276] Corannulene (compound 10) (100 mg, 0.4 mmol), N,N'-bis(2,6-diisopropylphenyl)triazene (compound 11) (182.8 mg, 0.5 mmol), and potassium hexafluorophosphate (KPF6) (101.2 mg, 0.55 mmol) were dissolved in tetrahydrofuran (THF) (2.25 mL). The solution was cooled to -78 °C. Then, 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) (53.2 μL, 0.5 mmol) and tert-butyl hypochlorite (t-BuOCl) (57.7 μL, 0.5 mmol) were added in the dark and stirred for 12 hours. The reaction solution was gradually returned to room temperature. The mixture was filtered and washed with CHCl. ​​The filtrate was evaporated under reduced pressure to obtain the crude product. Diethyl ether (Et2O) was added to the obtained crude product, and the mixture was purified by trituration to obtain PKO021 (308 mg, >99%). 1 H NMR (500 MHz, CDCl3) δ 7.85 (d, J = 8.9 Hz, 2H), 7.75 (d, J = 8.9 Hz, 2H), 7.68 (t, J = 7.9 Hz, 2H), 7.62 (d, J = 8.3 Hz, 2H), 7.57 (d, J = 7.7 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 7.02 (s, 2H), 6.77 (d, J = 8.3 Hz, 2H), 3.42-3.37 (m, 2H), 2.81-2.75 (m, 2H), 1.65 (d, J = 7.0 Hz, 6H), 1.36 (d, J = 6.6 Hz, 6H), 1.10 (d, J = 6.9 Hz, 6H), 0.61 (d, J = 6.6 Hz, 6H).

[0277] Synthesis Example 7: Synthesis of RKO022

[0278]

[0279] Corannulene (compound 10) (100 mg, 0.4 mmol), N,N'-bis(2,6-diisopropylphenyl)triazene (compound 11) (365.6 mg, 1.0 mmol), and potassium hexafluorophosphate (KPF6) (202.5 mg, 1.1 mmol) were dissolved in tetrahydrofuran (THF) (4.5 mL). The solution was cooled to -78 °C. Then, in the dark, 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) (106.4 μL, 1.0 mmol) and tert-butyl hypochlorite (t-BuOCl) (115.4 μL, 1.0 mmol) were added and stirred for 12 hours. The reaction solution was gradually returned to room temperature. The mixture was filtered and washed with CHCl. ​​The filtrate was evaporated under reduced pressure to obtain the crude product. Diethyl ether (Et2O) was added to the obtained crude product, and the mixture was purified by trituration to obtain PKO022 (442.9 mg, 83%). 1 H NMR (600 MHz, CDCl3) δ 7.74 (d, J = 8.2 Hz, 2H), 7.67 (t, J = 7.9 Hz, 2H), 7.63 (t, J = 7.7 Hz, 2H), 7.53 (d, J = 7.2 Hz, 2H), 7.50 (d, J = 7.6 Hz, 2H), 7.28 (s, 2H), 6.93 (d, J = 8.6 Hz, 2H), 6.84 (d, J = 13.2 Hz, 2H), 6.69 (d, J = 14.1 Hz, 2H), 6.60 (s, 2H), 3.26-3.20 (m, 4H), 2.72-2.68 (m, 2H), 2.65-2.59 (m, 2H), 1.56-1.55 (m, 6H), 1.50 (d, J = 6.2 Hz, 6H), 1.29 (d, J = 6.6, 6H), 1.28 (d, J = 6.6 Hz, 2H) 1.12 (d, J = 6.9 Hz, 6H), 1.10 (d, J = 6.9 Hz, 6H), 0.82 (d, J = 6.5 Hz, 6H), 0.56 (d, J = 6.5 Hz, 6H).

[0280] Synthesis Example 8: Synthesis of RKO088

[0281]

[0282] Pyrene (compound 12) (50 mg, 0.25 mmol), N,N'-bis(2,6-diisopropylphenyl)triazene (compound 11) (135.4 mg, 0.37 mmol), and potassium hexafluorophosphate (KPF6) (72.7 mg, 0.4 mmol) were dissolved in tetrahydrofuran (THF) (4.0 mL). The solution was cooled to -78 °C. Then, in the dark, 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) (39 μL, 0.37 mmol) and tert-butyl hypochlorite (t-BuOCl) (44.7 μL, 0.4 mmol) were added and stirred for 12 hours. The reaction solution was gradually returned to room temperature. The mixture was filtered and washed with CHCl. ​​The filtrate was evaporated under reduced pressure to obtain the crude product. Diethyl ether (Et2O) was added to the obtained crude product, and the mixture was purified by trituration to obtain PKO088 (98.5 mg, 52%). 1 H NMR (500 MHz, CDCl3) δ 7.94 (dd, J = 8.0, 1.1 Hz, 2H), 7.84 (s, 2H), 7.63 (t, J = 7.9 Hz, 2H), 7.55 (dd, J = 7.9, 1.3 Hz, 2H), 7.42 (t, J = 7.7 Hz, 2H), 7.29 (s, 2H), 7.14 (dd, J = 7.7, 1.1 Hz, 2H), 6.89 (d, J = 6.3 Hz, 2H), 3.49-3.41 (m, 2H), 1.71 (d, J = 6.6 Hz, 6H), 1.65-1.68 (m, 2H), 1.33 (d, J = 7.0 Hz, 6H), 0.78 (d, J = 6.9 Hz, 6H), 0.29 (d, J = 6.6 Hz, 6H).

[0283] Synthesis Example 9: Synthesis of RKO107

[0284]

[0285] Pyrene (compound 12) (10 mg, 0.049 mmol), N,N'-bis(2,6-diisopropylphenyl)triazene (compound 11) (179 mg, 0.49 mmol), and potassium hexafluorophosphate (KPF6) (95.7 mg, 0.52 mmol) were dissolved in tetrahydrofuran (THF) (4.0 mL). The solution was cooled to -78 °C. Then, in the dark, 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) (51.6 μL, 0.49 mmol) and tert-butyl hypochlorite (t-BuOCl) (58.8 μL, 0.52 mmol) were added and stirred for 12 hours. The reaction solution was gradually returned to room temperature. The mixture was filtered and washed with CHCl. ​​The filtrate was evaporated under reduced pressure to obtain the crude product. Diethyl ether (Et2O) was added to the obtained crude product, and the mixture was purified by trituration to give PKO107 (68.8 mg, >99%). 1 H NMR (500 MHz, CDCl3) δ 7.61 (t, J = 7.7 Hz, 4H), 7.47 (t, J = 7.6 Hz, 4H), 7.20 (d, J = 7.7 Hz, 4H), 7.02 (brs, 4H), 6.95 (t, J = 7.5, 1H), 6.68 (d, J = 7.7 Hz, 4H), 3.15-3.21 (m, 4H), 1.81-1.73 (m, 4H), 1.63 (d, J = 6.6 Hz, 12H), 1.32-1.28 (m, 12H), 0.87 (d, J = 6.9 Hz, 12H), 0.63 (d, J = 6.6 Hz, 12H).

[0286] Synthesis Example 10: Synthesis of RKO122

[0287]

[0288] Anthracene (compound 13) (10 mg, 0.056 mmol), N,N'-bis(2,6-diisopropylphenyl)triazene (compound 11) (308 mg, 0.84 mmol), and potassium hexafluorophosphate (KPF6) (155 mg, 0.84 mmol) were dissolved in tetrahydrofuran (THF) (4.0 mL). The solution was cooled to -78 °C. Then, in the dark, 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) (88.6 μL, 0.84 mmol) and tert-butyl hypochlorite (t-BuOCl) (95.2 μL, 0.84 mmol) were added and stirred for 12 hours. The reaction solution was gradually returned to room temperature. The mixture was filtered and washed with CHCl. ​​The filtrate was evaporated under reduced pressure to obtain the crude product. Diethyl ether (Et2O) was added to the obtained crude product, and the mixture was purified by trituration to give RKO122 (74 mg, 85%). 1 H NMR (500 MHz, CDCl3) δ 7.63 (t, J = 7.9 Hz, 2H), 7.54-7.41 (m, 8H), 7.38 (d, J = 7.4 Hz, 3H), 7.08 (d, J = 7.4 Hz, 2H), 6.72 (d, J = 14.9 Hz, 2H), 6.57 (d, J = 10.3 Hz, 2H), 6.53 (s, 2H), 6.30-6.23 (m, 2H), 5.61 (dd, J = 10.0, 2.9 Hz, 2H), 3.35-3.25 (m, 2H), 3.02-2.95 (m, 2H), 2.55-2.45 (m, 2H), 1.88-1.82 (m, 2H), 1.62 (d, J = 6.3 Hz, 6H), 1.52 (d, J = 6.6 Hz, 6H), 1.34 (d, J = 6.9 Hz, 6H), 1.28 (d, J = 6.6 Hz, 6H), 1.21 (d, J = 7.0 Hz, 6H), 1.09 (d, J = 6.5 Hz, 6H), 0.89 (d, J = 6.5 Hz, 6H), 0.41 (d, J = 6.6 Hz, 6H).

[0289] Test Example 1: Fluorescent Protein R-PE Transport Test Examples 1-2 and Comparative Examples 1-2 A solution (0.1 mg / mL, 2.5 μL) of the anionic fluorescent protein R-PE (R-phycoerythrin) was diluted with 20 mM HEPES-buffered saline (pH 7.4, 22.5 μL), and a dimethylformamide solution (0.5 mmol / L, 2 μL) of the polycyclic aromatic compound (KTU207, KTU059, or KTU205) obtained in Synthesis Examples 1-3 was added. The mixture was allowed to stand at room temperature for 15 minutes to complex the aromatic compound with R-PE. However, in Comparative Example 1, no polycyclic aromatic compound was used, and only dimethylformamide was used. In Comparative Example 2, PULSin, a commercially available protein transport material, was used instead of the polycyclic aromatic compound. Then, 225 μL of Dulbecco's modified Eagle's medium (DMEM, Wako) was added, and the resulting complex solution was added to HeLa cells (mammalian cells). After 4 hours, live imaging observation was performed. The results are shown in Figure 1.

[0290] In FIG. 1 , Comparative Example 1: R-PE+DMF Comparative Example 2: R-PE+PULSin Example 1: R-PE+KTU207 (Synthesis Example 1) Example 2: R-PE+KTU205 (Synthesis Example 3) Reference Example 1: PBS(−)+KTU207 (Synthesis Example 1)

[0291] As a result, it can be seen that in Comparative Example 1, the protein alone cannot move into the cells. Furthermore, in Reference Example 1, it can be seen that the protein transport material of the present invention alone does not emit fluorescence inside the cells. In contrast, in Examples 1 and 2, fluorescence could be confirmed inside the cells, suggesting that the use of the protein transport material of the present invention, which has cationic groups, allows the anionic protein R-PE to be introduced into the cells. In contrast, in Comparative Example 2, it can be seen that the protein transport material of the present invention has superior protein transport efficiency into the cells, even compared to commercially available PULSin.

[0292] Test Example 2: Transport Test of Hydrolytic Enzyme β-Galactosidase (Part 1) Examples 3 to 5 and Comparative Examples 3 to 5 A solution (4 mg / mL, 0.6 μL) of β-galactosidase (β-Gal), an anionic hydrolase, was dissolved in 20 mM HEPES-buffered saline (pH 7.4, 24.4 μL), and a dimethylformamide solution (0.5 mmol, 2 μL) of the polycyclic aromatic compound (KTU207, KTU059, KTU205, LHI, or LHII) obtained in Synthesis Examples 1 to 5 was added. The mixture was allowed to stand at room temperature for 10 minutes to complex the polycyclic aromatic compound and β-galactosidase. However, in Comparative Example 1, no polycyclic aromatic compound was used, and only dimethylformamide was used. In Comparative Example 2, PULSin, a commercially available protein transport material, was used instead of the polycyclic aromatic compound. Then, 500 μL of Dulbecco's modified Eagle's medium (DMEM, Wako) was added, and the resulting complex solution was added to HeLa cells (mammalian cells). After 4 hours, the cells were fixed with 4% paraformaldehyde (PFA) and treated with 5-bromo-4-chloro-3-indolyl-β-D-galactoside. The results are shown in Figure 2.

[0293] In FIG. 2 , Comparative Example 3: β-Gal + DMF Comparative Example 4: β-Gal + PULSin Comparative Example 5: β-Gal + Pro-DeliverIN Example 3: β-Gal + KTU207 (Synthesis Example 1) Example 4: β-Gal + KTU059 (Synthesis Example 2) Example 5: β-Gal + KTU205 (Synthesis Example 3)

[0294] As a result, it can be understood that the protein alone did not produce blue pigment upon addition of 5-bromo-4-chloro-3-indolyl-β-D-galactoside in Comparative Example 3, indicating that the protein could not be transported into the cells. In contrast, in Examples 4 to 8, the protein transport material of the present invention having a cationic group produced blue pigment upon addition of 5-bromo-4-chloro-3-indolyl-β-D-galactoside, suggesting that the anionic protein β-Gal was introduced into the cells.

[0295] Test Example 3: Transport Test of Fluorescently Labeled Antibody Examples 6-7 and Comparative Examples 6-7 A dimethylformamide solution (2 μL) of the polycyclic aromatic compounds (SMZ034, SMZ040) obtained in Synthesis Examples 4-5 was added to a fluorescently labeled antibody solution (0.1 mg / mL, 2.5 μL). The mixture was allowed to stand at room temperature for 15 minutes to conjugate the polycyclic aromatic compound and antibody. However, in Comparative Example 8, no polycyclic aromatic compound was used, and only dimethylformamide was used. In Comparative Example 9, Ab-DeliverIN, a commercially available protein transport material, was used instead of the polycyclic aromatic compound. 225 μL of Dulbecco's Modified Eagle's Medium (DMEM, Wako) was then added, and the resulting conjugate solution was added to HeLa cells (mammalian cells). After 4 hours, live imaging observation was performed. The fluorescently labeled antibody solution used was Invitrogen's Goat anti-Rabbit IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor Fluorescent TM 647, and the fluorescent dye Alexa Fluor TM The antibody solution was labeled with 647. The results are shown in Figure 3.

[0296] In FIG. 3, Comparative Example 6: antibody + DMF Comparative Example 7: antibody + Ab-DeliverIN Example 6: antibody + 0.5 mM SMZ034 (Synthesis Example 4) Example 7: antibody + 2.0 mM SMZ040 (Synthesis Example 5)

[0297] As a result, in Comparative Example 6, no clear fluorescence was observed with the antibody alone, indicating that it could not be transported into cells. In contrast, in Examples 6 and 7, it is suggested that even in the case of cationic proteins, the use of a polycyclic aromatic compound containing an anionic group can effectively transport the protein into cells and make it fluoresce effectively. Furthermore, compared to Comparative Example 7, in which Ab-DeliverIN was used, the number of cells into which the protein was introduced was greater, making it more suitable for observation.

[0298] Test Example 4: Trypsin Transport Test Examples 8-10 and Comparative Examples 8-9 A dimethylformamide solution (0.5 mmol, 2 μL) of the polycyclic aromatic compound (KTU207, SMZ034, or SMZ040) obtained in Synthesis Examples 1, 4, and 5 was added to an aqueous trypsin solution (0.8 mg / mL, 2.5 μL). The mixture was allowed to stand at room temperature for 10 minutes to complex the polycyclic aromatic compound with trypsin. However, in Comparative Examples 8 and 9, no polycyclic aromatic compound was used, and only dimethylformamide was used. As a reference example, a polycyclic aromatic compound was added to a PBS aqueous solution without trypsin. Subsequently, 500 μL of Dulbecco's modified Eagle's medium (DMEM, Wako) was added, and the resulting complex solution was added to HeLa cells (mammalian cells). After 6 hours, cell viability was measured by MTT assay. The results are shown in FIG. 4.

[0299] In FIG. 4 , the following means: Comparative Example 8: trypsin + DMF Example 8: trypsin + SMZ034 (Synthesis Example 4) Example 9: trypsin + SMZ040 (Synthesis Example 5) Example 10: trypsin + STU207 (Synthesis Example 1) Comparative Example 9: PBS(-) + DMF Reference Example 2: PBS(-) + SMZ034 (Synthesis Example 4) Reference Example 3: PBS(-) + SMZ040 (Synthesis Example 5) Reference Example 4: PBS(-) + KTU207 (Synthesis Example 1)

[0300] As a result, it can be seen that the protein transport material of the present invention has low cytotoxicity and is suitable for introduction into the living body.

[0301] Test Example 5: Transport test of hydrolase β-galactosidase (part 2) Examples 11 to 15 A solution (4 mg / mL, 0.6 μL) of β-galactosidase (β-Gal), an anionic hydrolase, was dissolved in 20 mM HEPES-buffered saline (pH 7.4, 24.4 μL), and a dimethylformamide solution (0.5 mmol, 2 μL) of the polycyclic aromatic compound (RKO021, RKO022, RKO088, RKO088, or RKO022) obtained in Synthesis Examples 6 to 10 was added. The polycyclic aromatic compound and β-galactosidase were complexed by leaving the mixture at room temperature for 10 minutes. Then, 500 μL of Dulbecco's modified Eagle's medium (DMEM, Wako) was added, and the resulting complex solution was added to HeLa cells (mammalian cells). After 4 hours, the cells were fixed with 4% paraformaldehyde (PFA) and treated with 5-bromo-4-chloro-3-indolyl-β-D-galactoside. The results are shown in Figure 5.

[0302] In FIG. 5 , Example 11: β-Gal+RKO021 (Synthesis Example 6) Example 12: β-Gal+RKO022 (Synthesis Example 7) Example 13: β-Gal+RKO088 (Synthesis Example 8) Example 14: β-Gal+RKO088 (Synthesis Example 9) Example 15: β-Gal+RKO122 (Synthesis Example 10)

[0303] As a result, in all Examples, the presence of a specific triazole skeleton resulted in the production of a blue pigment upon addition of 5-bromo-4-chloro-3-indolyl-β-D-galactoside, suggesting that the anionic protein β-Gal was introduced into cells.

[0304] Example 16 The following compounds were synthesized in the same manner as in Synthesis Examples 7 to 11 according to the following synthesis methods.

[0305]

[0306] These compounds were also tested in the same manner as above, and were confirmed to be capable of transporting proteins.

Claims

1. A protein transport material containing a polycyclic compound, the polycyclic compound being represented by general formula (1): [In the formula, Ar １ represents a fused aromatic ring which may have a substituent, provided that when R is a group having a primary, secondary or tertiary amino group; or a group having a nitrogen cation-containing group, Ar １ is a fused aromatic ring other than a perylene diimide ring which may have a substituent. R represents an anionic group or a cationic group. n represents an integer of 1 or more. When n is an integer of 2 or more, the n Rs may be the same or different.] or is represented by general formula (5): [In the formula, R １７ and R １８ and each of the anionic group or cationic group in the general formula (1) is represented by the general formula (2A) or (2B): [In the formula, Ar ２ represents an aromatic ring which may have a substituent. ３ and R ４ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar ２ represents an aromatic ring other than a perylene diimide ring which may have a substituent. ３ represents a nitrogen-containing heterocycle which may have a substituent, provided that R ３ and R ４ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar ３ R is a nitrogen-containing heterocycle other than a perylene diimide ring which may have a substituent. ３ represents a carboxy group; a primary, secondary, or tertiary amino group; a nitrogen cation-containing group; a sulfo group; a phosphate group; an ammonium group; a phosphonium group; or a sulfonium group. ４ represents a hydrogen atom or a hydrocarbon group; and Y represents a bond or a divalent group.

2. The polycyclic compound represented by the general formula (1) is represented by the general formula (1A): [In the formula, Ar １ represents a fused aromatic ring which may have a substituent, provided that R １ and R ２ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar １ R is a fused aromatic ring other than a perylene diimide ring which may have a substituent. １ and R ２ are the same or different and represent an anionic group or a cationic group.], and the anionic group or the cationic group in the general formula (1A) is represented by the general formula (2A) or (2B): [In the formula, Ar ２ represents an aromatic ring which may have a substituent. ３ and R ４ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar ２ represents an aromatic ring other than a perylene diimide ring which may have a substituent. ３ represents a nitrogen-containing heterocycle which may have a substituent, provided that R ３ and R ４ is a group having a primary, secondary, or tertiary amino group; or a group having a nitrogen cation-containing group, then Ar ３ R is a nitrogen-containing heterocycle other than a perylene diimide ring which may have a substituent. ３ represents a carboxy group; a primary, secondary, or tertiary amino group; a nitrogen cation-containing group; a sulfo group; a phosphate group; an ammonium group; a phosphonium group; or a sulfonium group. ４ represents a hydrogen atom or a hydrocarbon group; and Y represents a bond or a divalent group.

3. The group represented by the general formula (2A) is a group represented by the general formula (2A'): [In the formula, Ar ２ and Y is the same as above.] The protein transport material according to claim 2 .

4. The Ar １ The protein transport material of claim 1 , wherein is a fused aromatic hydrocarbon ring.

5. The above R ３ is a carboxy group, a primary amino group, an optionally substituted imidazolium group, an optionally substituted pyridinium group, an optionally substituted tetraalkylammonium group, or an optionally substituted triazolium group.

6. Ar in the general formula (1) １ The protein transport material according to claim 1, wherein the number of fused aromatic rings as the ring unit is 2 to 10.

7. A polycyclic compound having one or two structures represented by the general formula (5) in the main skeleton, represented by the general formula (5'): [In the formula, R １７ and R １８ R may be the same or different and represent an aryl group which may have a substituent. １９ , R ２０ , R ２１ and R ２２ are the same or different and represent a hydrogen atom, an alkyl group which may have a substituent, or an aryl group which may have a substituent. １９ and R ２０ , R ２０ and R ２１ , and R ２１ and R ２２ are joined together to form an aromatic ring at at least one position, and may be joined together to form a ring at other positions.

8. In the general formula (5'), R １９ and R ２０ , R ２０ and R ２１ , and R ２１ and R ２２ The protein transport material according to claim 7, wherein the number of aromatic rings formed at at least one site is 1 to 10.

9. The protein transport material of claim 1, further comprising a physiological buffer solution having a pH of 6.0 to 8.

0.

10. The protein transport material according to claim 1, which is a protein transport material for at least one cell selected from the group consisting of mammalian cells, plant cells, insect cells and Escherichia coli.

11. A pharmaceutical composition comprising the protein transport material according to any one of claims 1 to 10 and a protein.

12. A composition for genome editing comprising the protein transport material described in any one of claims 1 to 10 and a protein.

13. General formula (1'): [In the formula, Ar １ R′ represents a fused aromatic ring other than a perylene diimide ring, which may have a substituent. (In the formula, Ar ２ represents an aromatic ring which may have a substituent. Y represents a bond or a divalent group. ) represents a group represented by the following formula: n represents an integer of 1 or more. When n is an integer of 2 or more, the n Rs may be the same or different. ] or is represented by the following formula (5'): [In the formula, R １７ and R １８ R may be the same or different and represent an aryl group which may have a substituent. １９ , R ２０ , R ２１ and R ２２ are the same or different and represent a hydrogen atom, an alkyl group which may have a substituent, or an aryl group which may have a substituent. １９ and R ２０ , R ２０ and R ２１ , and R ２１ and R ２２ are joined together to form an aromatic ring at at least one position, and may be joined together to form a ring at other positions.

14. The polycyclic compound represented by the general formula (1) is represented by the general formula (1A'): [In the formula, Ar １ represents a fused aromatic ring which may have a substituent. １’ and R ２’ are the same or different and are represented by the general formula (2A'): (In the formula, Ar ２ represents an aromatic ring which may have a substituent; Y represents a bond or a divalent group; and represents a group represented by the following formula:

15. The polycyclic compound represented by the general formula (1') is a compound represented by the general formula (1A1'): [In the formula, R １ ' and R ２ ' are the same or different and represent a group represented by the general formula (2A'): (In the formula, Ar ２ represents an aromatic ring which may have a substituent; Y represents a bond or a divalent group; R represents a group represented by the formula: ５ , R ６ , R ７ and R ８ are the same or different and represent a hydrogen atom, a hydroxyl group, a halogen atom, an alkyl group, an alkoxy group, an aryl group, or an alkoxycarbonyl group. ５ , R ６ , R ７ and R ８ and at least one of the groups represents a hydroxyl group, an alkoxy group, or an alkoxycarbonyl group.

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