JPH09176204A - Functional material containing sialoglycochain and its synthesis - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a functional material contag. sialoglycochain, which is easy to be synthesized and utilized as a biomodel, etc., for its excellent orientation in water, and a synthesis method therefor. SOLUTION: A functional material contg. sialoglycochain monomer is synthesized by reacting a compd. having an amino group and a compd. having sialoglycochain at 0-50 deg.C by adding an activating reagent to bond the amino group of the compd. contg. an amino group and the carboxyl group of the compd. contg. sialoglycochain by dehydrocondensation. A polymer of the functional material contg. sialoglycochain is obtd. by polymerization or copolymerization of the monomer. The material obtd. has highly concentrated glycochain signal oriented on the solid surface and can be used as a biomedical material, etc.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a functional substance containing a sialo-glycan used as a biomedical material, an intermediate for producing the same, and a synthetic method thereof.

[0002]

The present inventor has been developing new biomedical materials utilizing the cell recognition function of oligosaccharides, and has already succeeded in synthesizing polyacrylamide and polystyrene in which oligosaccharide chains are linked to side chains. ing. In addition, focusing on the fact that sialic acid and its oligosaccharides, which are particularly important among sugar chains, are involved in various life phenomena, R.Roy has described the synthesis of polyacrylamide in which sialo sugar chains are linked to side chains.
There is a report from them.

However, sialo-oligosaccharide-containing polyacrylamide has poor orientation because both the sialo-oligosaccharide and the polyacrylamide are hydrophilic, and it is difficult to form a stable tissue in water. For this reason, it is not suitable for use as a biological model or as a virus trap.

In order to synthesize a polyacrylamide containing a sialo-oligosaccharide, first, of the functional groups of a compound having a sialo-oligosaccharide, a functional group which is not desired to be involved in the reaction is blocked with a protecting group, and then the sialo-oligosaccharide is attached There is also a problem that the synthesis process is very complicated because it requires a reaction of three or more steps of binding the hydroxyl group of the compound having with the polyacrylamide and then removing the protecting group again.

[0005]

DISCLOSURE OF THE INVENTION The present invention solves the above-mentioned conventional problems, is easy to synthesize, and has an excellent orientation in water, and therefore has a sialo-glycan-containing function that is easy to use as a biological model or the like. The purpose of the present invention is to provide a sexual substance and a method for synthesizing the same.

[0006]

The functional substance containing a sialo-oligosaccharide according to claim 1 made to solve the above-mentioned problems is a compound containing a sialo-oligosaccharide in an amino group of a compound having an amino group. It is characterized by comprising a monomer having a carboxyl group bonded thereto. Further, the functional substance containing a sialo-oligosaccharide according to the present invention comprises a polymer or copolymer of monomers in which the carboxyl group of the compound containing a sialo-oligosaccharide is bonded to the amino group of the compound having an amino group. It is a feature. The method for synthesizing a functional substance containing a sialo-oligosaccharide according to the third aspect of the present invention is the reaction of a compound having an amino group with a compound having a sialo-oligosaccharide at 0 ° C to 50 ° C to give an amino group of the compound having an amino group. In addition, a monomer having a carboxyl group of a compound containing a sialo-oligosaccharide bound thereto by dehydration condensation is obtained. This reaction can be carried out in one step. Further, the method for synthesizing the functional substance containing a sialo-oligosaccharide according to the invention of claim 5 is characterized in that the monomer obtained by the method of claim 3 is polymerized or copolymerized.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described below with reference to the model of FIG. In FIG. 1, 1 is a sialic acid monomer representing a compound having a sialo sugar chain, and 2 is P-vinylbenzylamine representing a compound having an amino group. When these are dissolved in a polar solvent such as dimethyl sulfoxide and then an activator is added and mixed, a condensation reaction proceeds between the carboxyl group of sialic acid and the amino group of P-vinylbenzylamine, resulting in a sialo sugar chain. Vinyl monomer 3 having a side chain is produced in one step. This reaction can be carried out in a temperature range of about 0 ° C to 50 ° C, more preferably near room temperature of 20 to 35 ° C in a short time. The reaction temperature was set to 0 ° C to 50 ° C because if the reaction temperature is lower than 0 ° C, the reaction will not proceed easily, and if the reaction temperature exceeds 50 ° C, an undesirable side reaction may occur. is there. The vinyl monomer 3 having this side chain as a sialo sugar chain can be used as a functional substance containing a sialo sugar chain itself. Further, by polymerizing or copolymerizing the vinyl monomer 3 having this sialo-oligosaccharide as a side chain by a conventional method, a functional substance containing a sialo-oligosaccharide, which is a polymer of 4, can be obtained.

As the above-mentioned compound having a sialo-oligosaccharide, sialic acid, a sialic acid derivative, or sugars, glycoproteins, glycolipids containing these and the like can be used. In particular, if an oligomer of sialic acid is used, a functional substance containing a sialo-sugar chain having a plurality of carboxyl groups that do not participate in the condensation reaction with an amide group can be obtained. Therefore, these carboxyl groups have a high function as a sugar chain recognition signal. Has the advantage that it can be expressed.

As the compound having an amino group, in addition to vinylbenzylamine, vinyl compounds such as vinylaniline and allylamine, phenylamine, N-hexadecylamine, double-chain alkylamine and the like can be used. The chemical structural formulas of these compounds are shown in Chemical formula 1.

[0010]

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As the activator, for example, BO shown in Chemical formula 2
P, PyBOP, DBP, HOBt, HBTU, etc. can be used. Although the activator has an action of promoting the reaction, the use of the activator is not essential in the present invention because the reaction proceeds if the reaction time is sufficiently long.

[0012]

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Since the functional substance containing a sialo-oligosaccharide thus obtained is composed of a hydrophilic sialo-oligosaccharide and a hydrophobic functional group, it is easy to orient in water as shown in FIG. It is easy to stick to. For this reason, the sugar chain signal is oriented to the solid surface and the membrane surface at an extremely high concentration, and is suitable for use as a biological model with high biorecognition ability, or as a cell culture substrate or a virus trap. Is.
The functional substance containing a sialo-oligosaccharide obtained by combining a sialo-oligosaccharide with a linear alkylamine or cholesterol having an amino group forms micelles in water as shown in FIG. It can be incorporated into a membrane or liposome to form a recognition function membrane, and can also be used as a raw material for drug delivery. Further, according to the present invention, since the reaction can proceed without using a protecting group as in the conventional case, a functional substance having a sialo-oligosaccharide can be synthesized very easily.

[0014]

Next, examples of the present invention will be described. Sialic acid (150 mg, 0.5 mmol) was placed in a 100 mL eggplant-shaped flask, and 3.5 mL of dimethyl sulfoxide was added and dissolved. As a carboxyl group activator, BOP: Benzotriazol-l-oxy-tris
(dimethylamino) phosphonium hexafluorophosphate (665
mg, 1.50 mmol) and HOBT: l-Hydroxybenzotriazol
e (67.5 mg, 0.50 mmol) was added, and the mixture was reacted at room temperature for 1 hour. The reaction was stopped by adding 25 mL of water. A precipitate was formed in the reaction solution, which was removed by suction filtration.

The obtained solution was concentrated under reduced pressure and then purified by column chromatography while changing the developing solvent. The packing material is Toyopearl-HW-40s and the developing solvent is 1
1st time: Methanol: water = 4: 1, 2nd time: water, 3rd time:
Methanol: water = 4: 1. The wavelength of the UV detector is 280 nm. The fraction containing the target substance was concentrated under reduced pressure, and then the aqueous solution was freeze-dried to obtain the target substance (a vinyl monomer having a sialo sugar chain as a side chain). The yield is 0.154 g, and the yield is 75%. The data obtained by analyzing this object by nuclear magnetic resonance is shown in Equation 1. This was polymerized by a conventional method to obtain a polymeric sialo-glycan-containing functional substance.

[0016]

(Equation 1)

[0017]

Industrial Applicability As described above, according to the present invention, a functional substance containing a sialo-oligosaccharide, which is a monomer having a sialo-oligosaccharide as a side chain, can be synthesized in one step without using a conventional protecting group. Further, by polymerizing or copolymerizing this by a conventional method, a functional substance having a sialo-oligosaccharide as a polymer can be easily obtained. In particular, when the functional substance containing sialo-oligosaccharide has a hydrophilic group and a hydrophobic group, the sugar chain signal is oriented to the solid surface at an extremely high concentration as shown in FIG. 2, and as shown in FIG. Since it is capable of forming micelles in, it is suitable for use as a biological model with high biorecognition ability, or as a cell culture substrate, virus trap, drug delivery material, and the like.

[Brief description of the drawings]

FIG. 1 is a process explanatory view showing a synthesis process of the present invention.

FIG. 2 is a conceptual diagram showing an orientation state of a functional substance containing a sialo-oligosaccharide.

FIG. 3 is a conceptual diagram showing a state in which a functional substance containing a sialo-oligosaccharide forms micelles.

[Explanation of symbols]

1 Sialic acid monomer representative of compounds with sialo-sugar chains, P-vinylbenzylamine representative of compounds with 2 amino groups, 3 Vinyl monomers with side chains of sialo-sugar chains, 4 Sialo-sugar chain-containing functional substances

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Yuuji Kawase No. 56 Sudamachi, Mizuho-ku, Nagoya-shi, Aichi Prefecture Nikko Insulators Co., Ltd. No. 56 Nihon Insulator Co., Ltd.

Claims (5)

[Claims] 1. A functional substance containing a sialo sugar chain, which comprises a monomer in which a carboxyl group of a compound containing a sialo sugar chain is bonded to an amino group of a compound having an amino group. 2. A functional substance containing a sialo-oligosaccharide, comprising a polymer or copolymer of monomers in which a carboxyl group of a compound containing a sialo-oligosaccharide is bonded to an amino group of a compound having an amino-group. 3. A compound having an amino group and a compound having a sialo sugar chain are reacted at 0 ° C. to 50 ° C., and the carboxyl group of the compound having a sialo sugar chain is dehydrated and condensed to the amino group of the compound having an amino group. A method for synthesizing a functional substance containing a sialo-oligosaccharide, which comprises obtaining a bound monomer. 4. The method for synthesizing a functional substance containing a sialo-oligosaccharide according to claim 3, wherein the monomer is synthesized in one step. 5. A method for synthesizing a functional substance containing a sialo-oligosaccharide, which comprises polymerizing or copolymerizing the monomer obtained by the method according to claim 3.