CN114920672A - Preparation of S- (6-hexanol) -L-cysteine sulfoxide and application thereof in preventing and treating dental caries - Google Patents

Preparation of S- (6-hexanol) -L-cysteine sulfoxide and application thereof in preventing and treating dental caries Download PDF

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CN114920672A
CN114920672A CN202210592333.2A CN202210592333A CN114920672A CN 114920672 A CN114920672 A CN 114920672A CN 202210592333 A CN202210592333 A CN 202210592333A CN 114920672 A CN114920672 A CN 114920672A
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hexanol
cysteine
cysteine sulfoxide
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CN114920672B (en
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杨春玉
刘远翔
李春芳
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Shandong University
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    • C07C315/02—Preparation of sulfones; Preparation of sulfoxides by formation of sulfone or sulfoxide groups by oxidation of sulfides, or by formation of sulfone groups by oxidation of sulfoxides
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    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Abstract

The invention relates to the technical field of biological medicines, in particular to preparation of S- (6-hexanol) -L-cysteine sulfoxide and application thereof in preventing and treating dental caries. S- (6-hexanol) -L-cysteine sulfoxide has a coconut milk flavor and, after interaction with cysteine sulfoxide lyase, produces a trihexyl-sulfite that likewise has a coconut milk flavor, which has biological activity in killing Streptococcus mutans, while mutans streptococci cause dental caries, so that cysteine sulfoxide lyase is used in combination with S- (6-hexanol) -L-cysteine sulfoxide for the control of dental caries. The dry cysteine sulfoxide lyase powder and the S- (6-hexanol) -L-cysteine sulfoxide are added into milk powder and the like to be compounded into the milk tablet, and the milk tablet has good activity of inhibiting streptococcus mutans after being dissolved and has good application prospect in preventing and treating dental caries.

Description

Preparation of S- (6-hexanol) -L-cysteine sulfoxide and application thereof in preventing and treating dental caries
Technical Field
The invention relates to the technical field of biological medicines, in particular to preparation of S- (6-hexanol) -L-cysteine sulfoxide and application thereof in preventing and treating dental caries.
Background
The decayed tooth of children is commonly called as decayed tooth and is a common oral disease of children. The incidence of the caries of the children is the first of the diseases of the children, the incidence of the caries can reach more than 90 percent in the children, and the caries is the third disease which is listed as the key prevention and treatment by the world health organization after cardiovascular diseases and cancers. The main clinical manifestations of dental caries are progressive lesions of the hard tissues of the teeth, including inorganic demineralization and organic matter breakdown, which progress from color change to substantial lesions. Caries cannot be repaired by itself, and once the caries damages teeth, the teeth must be restored by means of repair treatment. When caries is decayed to reach the deep dentin layer close to the dental pulp or the dental pulp is affected, pulpitis or root canal inflammation is easy to cause, and no medicine can be used at the time, and only root canal treatment can be carried out.
Daily control of dental caries is very important. Research shows that the main dental caries pathogenic bacteria in the oral cavity are streptococcus mutans. The streptococcus mutans can generate glucan by using compounds such as sucrose and the like to grow and adhere pathogenic bacteria to form bacterial plaque, acid is generated in the deep layer of the bacterial plaque to attack teeth, and hard tissues of the teeth are demineralized and dissolved to generate caries holes. The current products for the control of streptococcus mutans or dental caries are largely divided into chemical and biological products. Such as biological enzyme, Chinese medicinal components, fluorine-containing toothpaste, collutory, or probiotic buccal tablet. Because the children have small age of decayed tooth onset and are the key period of decayed tooth prevention and treatment, the use of products such as toothpaste and the like in children has great limitation, the decayed tooth prevention and treatment effect is poor, and probiotics need certain growth conditions for playing the effect, so the defect of slow effect is existed.
The produced product diallyl thiosulfinate has good inhibition effect on streptococcus mutans by the biocatalysis of cysteine sulfoxide lyase from S-allyl-L-cysteine sulfoxide, the MIC value calculated according to the substrate S-allyl-L-cysteine sulfoxide is only 0.65 mug/ml, and the diallyl thiosulfinate has good application prospect in the development and application of oral cavity dental caries prevention and treatment products. However, the product diallyl thiosulfinate has a pungent taste and is not dispersed for a long time, which results in that the active ingredient diallyl thiosulfinate, although having a good bacteriostatic effect, is not suitable for oral cavity caries control. Therefore, a substrate is developed, and the thiosulfinate bactericidal substance which has fragrance, is mild and non-irritant is generated through enzyme catalysis, so that the thiosulfinate bactericidal substance has an important application value for preventing and treating the dental caries.
Disclosure of Invention
The invention aims to solve the problems in the prior art and provides preparation of S- (6-hexanol) -L-cysteine sulfoxide and application thereof in preventing and treating dental caries. Synthesizing cysteine-S-conjugate with coconut milk fragrance, compositely producing milk tablets by using cysteine sulfoxide lyase, a substrate, an additive and the like, and in-situ biocatalytically synthesizing a fragrance antibacterial thiosulfinate substance in an oral cavity, thereby realizing safe, rapid and effective prevention and treatment of pathogenic bacteria such as oral streptococcus mutans and the like.
The technical scheme of the invention is as follows:
preparation of S- (6-hexanol) -L-cysteine sulfoxide:
the raw material is L-cysteine, the substituent is 6-bromo-1-hexanol or 6-chloro-1-hexanol, and the preparation method comprises two steps of substitution reaction and oxidation reaction; the sample adding sequence of the substitution reaction system is as follows: ethanol water solution, sodium hydroxide, L-cysteine and substituent; in the process of the substitution reaction, adding sodium hydroxide into the ethanol water solution, and dissolving; adding L-cysteine, and dissolving; adding a substituent, stirring until the solution is transparent and clear, and stirring for 8-12 h; adjusting the pH of the solution (for example, with acetic acid) to 4-6 to precipitate a white solid S- (6-hexanol) -L-cysteine; wherein the ratio of ethanol: water is (4: 1) - (5: 1), sodium hydroxide is 0.8-4.5 mol/L, the addition amount of L-cysteine is 0.4-2.5 mol/L, and the addition amount of a substituent is consistent with the mole number of the addition amount of the L-cysteine, so that S- (6-hexanol) -L-cysteine is finally obtained; the oxidizing agent of the oxidation reaction is 30% of hydrogen peroxide, and the feeding ratio of the 30% of hydrogen peroxide to the S- (6-hexanol) -L-cysteine is as follows: (2: 1) - (5: 1) (V/m), the end point of the oxidation reaction is that S- (6-hexanol) -L-cysteine is completely dissolved, the heat release is stopped, and S- (6-hexanol) -L-cysteine sulfoxide is finally obtained.
The principle of the step is that S- (6-hexanol) -L-cysteine is difficult to dissolve in water, but S- (6-hexanol) -L-cysteine sulfoxide is easy to dissolve in water, hydrogen peroxide can oxidize S- (6-hexanol) -L-cysteine into S- (6-hexanol) -L-cysteine sulfoxide, and the reaction process is exothermic. The S- (6-hexanol) -L-cysteine sulfoxide finally prepared has coconut milk fragrance.
As a preferred technical scheme, the molecular weight of the S- (6-hexanol) -L-cysteine sulfoxide is 237.32, and the chemical formula is C 9 H 19 O 4 NS, the structural formula is shown as follows:
Figure BDA0003665918950000031
as a preferred embodiment, the substituent is 6-bromo-1-hexanol.
As a preferable technical proposal, the adding amount of the sodium hydroxide is 1.375mol/L, and the adding amount of the L-cysteine is 0.6875 mol/L.
The S- (6-hexanol) -L-cysteine sulfoxide synthesized by the chemical synthesis method has coconut fragrance or coconut milk fragrance, and is cleaved by cysteine sulfoxide lyase to generate dihexanol thiosulfinate with molecular weight of 282.46 and chemical formula C 12 H 26 O 3 S 2 The structural formula is as follows:
Figure BDA0003665918950000041
the dithiazolesulfonate ester of hexanol has bactericidal activity while still having a coconut milk flavor.
Based on the antibacterial mechanism and active antibacterial groups of the dihexyl sulphosulfinate, the effective substances for preventing and treating oral cavity decayed teeth are analyzed and determined to be sulphosulfinate substances, and the sulphosulfinate substances can be derived from bacteriaIs produced by the action of the cysteine sulfoxide lyase LCC1 with its substrate cysteine sulfoxide-S conjugate. Therefore, the desire to obtain scented thiosulfinate compounds requires first obtaining a scented cysteine sulfoxide-S conjugate. In grapes, a fragrant cysteine-S conjugate (3MH-cys), S- (3-hexanol) -L-cysteine, is present. When wine is made by fermentation using yeast, the C-S lyase in the yeast cleaves its beta-position to 3-mercaptohexanol, a substance with a volatile grapefruit aroma. Thus, if S- (3-hexanol) -L-cysteine is oxidized to S- (3-hexanol) -L-cysteine sulfoxide and then acted upon by the bacteria-derived cysteine sulfoxide lyase LCC1, a bis (3-hexanol) thiosulfinate would theoretically be produced, which is likely to have a flavor. If the substrate is synthesized by chemical synthesis, the key to the synthesis of S- (3-hexanol) -L-cysteine sulfoxide is the substitution reaction of cysteine with 3-bromohexanol as a substituent. However, 3-bromohexanol is not common and is not available commercially as a batch number, and the only substituent currently available is 6-bromo-1-hexanol, which, when substituted with L-cysteine, will form the S- (3-hexanol) -L-cysteine isomer, S- (6-hexanol) -L-cysteine, which, when oxidized, will form S- (6-hexanol) -L-cysteine sulfoxide. The molecular formula and molecular weight of the S- (6-hexanol) -L-cysteine sulfoxide are completely consistent with those of the S- (3-hexanol) -L-cysteine sulfoxide, and the chemical formulas are all C 9 H 19 O 4 NS, both molecular weights 237.32, is likely to also have an aroma.
The amino acid sequence of the used cysteine sulfoxide lyase LCC1 is as follows:
MRDSAAAQRLQAIREAMPATTAHTYLNTGTFGPLPRCVIEAMQERLQEEWREGRLGAEAHAALLSHYREARQRCAELFHADIEEIALTDNTGEGLNIIAFGLNWREGGEVITTNHEHISALAPLYQLRERYGIRLRIADLGERGERPAEEEIARLITPRTRLIVLSHVSFMTGARFDVSAVTALGRRHGLPVLVDGAQAAGAIAVDVQELDVDFYAFPMQKWLCGPDGTGGLYVRRTALGQVQSTYVGYYSLKHEHSGVWELQETAQRFELGGRQTAALVGQSRALRWLAEEVGHRWLQERIASLNRYAAELLSEVPGVKILTPQPGASGLLSFTFARAEPEAVVRRLAEEHNVLIRSIHERQALRLSTGFYNTEEELERVAAILRSWP，
s- (6-hexanol) -L-cysteine sulfoxide and cysteine sulfoxide lyase in the presence of H 2 Under the condition of participation of O, dihexyl sulphosulfenate is obtained, and can kill pathogenic bacteria such as streptococcus mutans. The cysteine sulfoxide lyase is bacterial source cysteine sulfoxide lyase and is obtained by heterologous expression of pichia pastoris.
The S-alkyl-L-cysteine sulfoxide lyase LCC1 is a cysteine sulfoxide lyase derived from bacteria, which functions as a plant cysteine sulfoxide lyase by cleaving the cysteine sulfoxide-S conjugate with the C-S at the β position to produce the R-sulfenic acid, which is then spontaneously dehydrocondensed to produce the "di-R-thiosulfinate", which is produced when the substrate for the enzyme is S- (6-hexanol) -L-cysteine sulfoxide. The product can effectively inhibit the growth of oral pathogenic bacteria such as Streptococcus mutans.
The S- (6-hexanol) -L-cysteine sulfoxide is compounded into milk tablets for preventing and treating decayed teeth, and the milk tablets are prepared from S- (6-hexanol) -L-cysteine sulfoxide, LCC1 spray-dried enzyme powder heterologously expressed by pichia pastoris, milk powder and xylitol. S- (6-hexanol) -L-cysteine sulfoxide: the mass ratio of the LCC1 dry enzyme powder is (1: 1) - (1: 5), and each milk tablet contains 0.1-1 mg of S- (6-hexanol) -L-cysteine sulfoxide. The mass ratio of the milk powder to the xylitol is 20: 1, each milk tablet contains 2-5 g of milk powder.
S- (6-hexanol) -L-cysteine sulfoxide can be cleaved to produce the trihexyl thiosulfinate using bacterial cysteine sulfoxide lyase. The DNPH method can be used for measuring the enzyme activity and the amount of the byproduct pyruvic acid, the product still has coconut milk fragrance after complete reaction can be smelled, and the enzyme and the substrate are found by a 96-well plate in-situ bacteriostatic experiment and have bacteriostatic activity. HPLC-MS detection shows that the prepared S- (6-hexanol) -L-cysteine sulfoxide has correct molecular weight, single peak and high purity.
Because the escherichia coli is used as an expression system of the enzyme to introduce the endotoxin, and the endotoxin removal process is high in cost and complicated, so that the application of the enzyme is limited, and pichia pastoris not generating endotoxin is selected as the expression system. The constructed pichia pastoris expresses a large amount of cysteine sulfoxide lyase LCC1, the cysteine sulfoxide lyase exists in fermentation supernatant, and after 15% of maltodextrin is added into the supernatant and is fully dissolved, spray drying of the cysteine sulfoxide lyase can be realized, so that dry enzyme powder of the cysteine sulfoxide lyase is obtained.
The self-made S- (6-hexanol) -L-cysteine sulfoxide, spray-dried enzyme powder, milk powder, xylitol and the like are mixed to be compounded into the oral cavity bacteriostatic and mothproof milk tablet. Each milk tablet comprises 0.1-1 mg of substrate S- (6-hexanol) -L-cysteine sulfoxide, 0.1-5 mg of cysteine sulfoxide lyase dry enzyme powder, 2-5 g of milk powder and 0.1g of xylitol. The milk tablet is dissolved and used for inhibiting streptococcus mutans which is a main pathogenic bacterium of dental caries, and can still have good antibacterial activity. The milk tablet has remarkable antibacterial effect, good taste, and convenient use for children, and can realize effective prevention and treatment of dental caries.
The invention has the beneficial effects that:
(1) the invention synthesizes a coconut milk flavor compound, namely, the dihexyl sulphosulfinate by taking S-alkyl-L-cysteine sulphoxide lyase LCC1 and a novel compound, namely S- (6-hexanol) -L-cysteine sulphoxide, as substrates through biocatalysis.
(2) The S- (6-hexanol) -L-cysteine sulfoxide and S-alkyl-L-cysteine sulfoxide cleavage enzyme have in-situ reaction, and the MIC value of the streptococcus mutans reaches 46 mu g/ml according to the calculation of the S- (6-hexanol) -L-cysteine sulfoxide, so that the streptococcus mutans has an obvious antibacterial function.
(3) The prepared milk tablet has milk flavor and strong bacteriostatic ability, and the MIC value of streptococcus mutans reaches 184 mug/ml, so that the effective prevention and treatment of dental caries can be realized.
(4) The preparation method of the substrate S- (6-hexanol) -L-cysteine sulfoxide is simple and convenient and has high purity.
(5) The reagent prepared from the substrate S- (6-hexanol) -L-cysteine sulfoxide has low cost, the reagent cost of 1g of the substrate is less than 5 yuan, and the reagent can be added into 4000-piece milk tablets.
Drawings
FIG. 1 is a structural formula of S- (6-hexanol) -L-cysteine sulfoxide as a substrate and a bishomogenothiosulfinate with coconut milk fragrance;
FIG. 2 is a HPLC-MS spectrum of homemade S- (6-hexanol) -L-cysteine sulfoxide;
FIG. 3 shows the results of bacteriostasis;
fig. 4 is a schematic diagram of a specific design scheme of the bacteriostatic milk tablet.
Detailed Description
In order to make the technical means, technical features, objects and technical effects of the present invention easily understandable, the present invention is further described below with reference to the specific drawings.
Example 1:
substrate preparation
The substrate is S- (6-hexanol) -L-cysteine sulfoxide, the structural formulas of the substrate and the product are shown in figure 1, and the preparation method is divided into two steps. The first step is the synthesis of S- (6-hexanol) -L-cysteine and the second step is the oxidation of S- (6-hexanol) -L-cysteine. First, the first step is carried out by mixing ethanol and water in a ratio of 5: 1, then adding 0.7mol of sodium hydroxide solid, stirring until the sodium hydroxide solid is completely dissolved, adding 0.3mol of L-cysteine, and stirring again until the sodium hydroxide solid is completely dissolved. Then 0.3mol of 6-bromo-1-hexanol is added, the mixture is stirred until the solution is transparent and clear, and the stirring is continued overnight for 12 hours by covering a sealing film. The pH of the solution was adjusted to 5.0 with acetic acid to precipitate a large amount of white S- (6-hexanol) -L-cysteine solid, which was left to stand for a while, and then the solid was collected by filtration and dried at 65 ℃ to obtain a product in a yield of 150% based on the specific gravity of the product and L-cysteine. The second reaction was carried out by taking 2g of the solid S- (6-hexanol) -L-cysteine prepared in the first step and adding 5ml of 30% hydrogen peroxide solution for oxidation, which was accompanied by an exotherm at the end of which the solid was completely dissolved and no longer exothermic, and a clear solution should be formed, and a large amount of white solid precipitated immediately after the addition of cold ethanol. The white solid was collected and filtered and dried at 65 ℃ to give the product S- (6-hexanol) -L-cysteine sulfoxide at 75% conversion and a combined yield of 112.5%.
Example 2:
HPLC-MS validation of homemade substrates
Preparing 0.5mg/ml 30% methanol aqueous solution from home-made S- (6-hexanol) -L-cysteine sulfoxide, and then sending to LCMS for identification, wherein the sample injection amount is 5ul, the detection wavelength is 214nm, the chromatographic column is a C18 column, the flow rate is 0.8ml/min, and the ion source is ESI positive ion. The mass spectrum result is shown in FIG. 2, the molecular weight of S- (6-hexanol) -L-cysteine sulfoxide is 237.32, and the positive ion bombardment result is 238.32. The molecular weight is correct, the mass spectrum result is a single peak, and the molecular weight at each position of the peak is the same along with the arrow movement, so the material purity is high.
Example 3:
preparation of milk slices
As shown in fig. 4, is a schematic diagram of a specific design scheme of the bacteriostatic milk tablet. The milk tablet for inhibiting Streptococcus mutans in oral cavity comprises milk powder (preferably skimmed milk powder), xylitol, cysteine sulfoxide lyase dry enzyme powder and substrate S- (6-hexanol) -L-cysteine sulfoxide. The amino acid sequence of the cysteine sulfoxide lyase is as follows: MRDSAAAQRLQAIREAMPATTAHTYLNTGTFGPLPRCVIEAMQERLQEEWREGRLGAEAHAALLSHYREARQRCAELFHADIEEIALTDNTGEGLNIIAFGLNWREGGEVITTNHEHISALAPLYQLRERYGIRLRIADLGERGERPAEEEIARLITPRTRLIVLSHVSFMTGARFDVSAVTALGRRHGLPVLVDGAQAAGAIAVDVQELDVDFYAFPMQKWLCGPDGTGGLYVRRTALGQVQSTYVGYYSLKHEHSGVWELQETAQRFELGGRQTAALVGQSRALRWLAEEVGHRWLQERIASLNRYAAELLSEVPGVKILTPQPGASGLLSFTFARAEPEAVVRRLAEEHNVLIRSIHERQALRLSTGFYNTEEELERVAAILRSWP the flow of the air in the air conditioner,
each milk tablet contains 2g of milk powder, 0.1g of xylitol, 1.5mg of cysteine sulfoxide lyase dry enzyme powder and 0.3mg of substrate. The raw materials are premixed and then compacted into tablets by using a tablet machine. The whole preparation process is kept dry. Because the enzyme reacts with the substrate in the presence of water, the product is expected to react in situ in the oral environment to produce the trihexyl sulphosulfinate. The product is eaten by slowly dissolving.
Example 4:
bacteriostatic test
MIC values were determined by double dilution in 96-well plates. Adjusting the tested streptococcus mutans bacterial liquid to have an absorbance value of 0.090-0.10 (detected by a UV-1700 ultraviolet-visible spectrophotometer) detected at a wavelength of 625nm by using sterilized normal saline, then diluting the sterilized BHI broth according to a ratio of 1:200, adding the bacteria-containing BHI broth into a 96-well plate, adding a substrate, a cysteine sulfoxide lyase enzyme liquid and a dissolved milk tablet, enabling a substrate S- (6-hexanol) -L-cysteine sulfoxide final concentration 1-11 hole to be 23552, 11776, 5888, 2944, 1472, 736, 368, 184, 92, 46, 23 mu g/ml and other series concentration 12 th hole to be blank control, using ampicillin (Amp) as a standard, enabling the initial concentration of Amp to be 250 mu g/ml, and standing and culturing at 37 ℃. (the corrected bacteria liquid should be inoculated within 30min, and the detection result is influenced by the overlong standing time of the corrected bacteria liquid)
And judging the result as the culture at 37 ℃ for 16-18 h, firstly observing the growth of bacteria in a positive control, observing the growth of no bacteria in a negative control (blank BHI broth), then observing the test sample, judging the growth of the bacteria to be turbid by naked eyes, judging the growth of the bacteria to be clear by the naked eyes, and judging the corresponding minimum sample concentration in the clear test tube as the MIC value. As shown in FIG. 3, S- (6-hexanol) -L-cysteine sulfoxide reacted with S-alkyl-L-cysteine sulfoxide cleavage enzyme in situ in 96-well plates to inhibit S.mutans. The milk tablet is prepared by pressing S- (6-hexanol) -L-cysteine sulfoxide and S-alkyl-L-cysteine sulfoxide lyase, and inhibiting streptococcus mutans after dissolving the milk tablet. Inhibition of streptococcus mutans by Amp.
The MIC values for this in situ reaction were calculated as the concentration of S- (6-hexanol) -L-cysteine sulfoxide, the MIC for S- (6-hexanol) -L-cysteine sulfoxide for inhibiting S.mutans in situ reaction with S-alkyl-L-cysteine sulfoxide lyase was 46. mu.g/ml, and the MIC for S- (6-hexanol) -L-cysteine sulfoxide for inhibiting S.mutans after dissolution of milk tablets pressed with S-alkyl-L-cysteine sulfoxide lyase was 184. mu.g/ml. The MIC of downstream Amp for S.mutans was 0.976. mu.g/ml.
The MIC value should be determined by the drug concentration in the last clear well, and the first few wells are turbid but sterile because of precipitation due to too high substrate concentration.
In summary, the embodiments of the present invention are merely exemplary embodiments, and are not intended to limit the scope of the present invention. All equivalent changes and modifications made according to the content of the claims of the present invention should fall within the technical scope of the present invention.

Claims (9)

  1. A process for the preparation of S- (6-hexanol) -L-cysteine sulfoxide, characterized by: the raw material is L-cysteine, the substituent is 6-bromo-1-hexanol or 6-chloro-1-hexanol, and the preparation method comprises two steps of substitution reaction and oxidation reaction; the sample adding sequence of the substitution reaction system is as follows: ethanol water solution, sodium hydroxide, L-cysteine and substituent; adding sodium hydroxide into the ethanol water solution, and dissolving; adding L-cysteine, and dissolving; adding a substituent, and stirring for 8-12 hours until the solution is transparent and clear; adjusting the pH value of the solution to be between 4 and 6 to precipitate white S- (6-hexanol) -L-cysteine solid, wherein the weight ratio of ethanol: water is (4: 1) - (5: 1), the addition amount of sodium hydroxide is 0.8-4.5 mol/L, the addition amount of L-cysteine is 0.4-2.5 mol/L, and the addition amount of a substituent is consistent with the mole number of the addition amount of the L-cysteine, so that S- (6-hexanol) -L-cysteine is finally obtained; the oxidizing agent of the oxidation reaction is 30% of hydrogen peroxide, and the feeding ratio of the 30% of hydrogen peroxide to the S- (6-hexanol) -L-cysteine is as follows: (2: 1) - (5: 1) (V/m), the end point of the oxidation reaction is that S- (6-hexanol) -L-cysteine is completely dissolved, the heat release is stopped, and S- (6-hexanol) -L-cysteine sulfoxide is finally obtained.
  2. 2. The process for the preparation of S- (6-hexanol) -L-cysteine sulfoxide according to claim 1, characterized in that: the structural formula of the S- (6-hexanol) -L-cysteine sulfoxide is shown as follows:
    Figure FDA0003665918940000011
  3. 3. the process for the preparation of S- (6-hexanol) -L-cysteine sulfoxide according to claim 1, characterized in that: the substituent is 6-bromo-1-hexanol.
  4. 4. The process for the preparation of S- (6-hexanol) -L-cysteine sulfoxide according to claim 1, characterized in that: the addition amount of sodium hydroxide is 1.375mol/L, and the addition amount of L-cysteine is 0.6875 mol/L.
  5. Use of S- (6-hexanol) -L-cysteine sulfoxide or cysteine sulfoxide lyase for the preparation of a medicament or a composition for the prevention or treatment of dental caries, characterized in that: cleavage of S- (6-hexanol) -L-cysteine sulfoxide by cysteine sulfoxide lyase LCC1 at the beta position produces a dithiazolesulfonate ester of the formula:
    Figure FDA0003665918940000021
    wherein the amino acid sequence of the cysteine sulfoxide lyase LCC1 is as follows:
    MRDSAAAQRLQAIREAMPATTAHTYLNTGTFGPLPRCVIEAMQERLQEEWREGRLGAEAHAALLSHYREARQRCAELFHADIEEIALTDNTGEGLNIIAFGLNWREGGEVITTNHEHISALAPLYQLRERYGIRLRIADLGERGERPAEEEIARLITPRTRLIVLSHVSFMTGARFDVSAVTALGRRHGLPVLVDGAQAAGAIAVDVQELDVDFYAFPMQKWLCGPDGTGGLYVRRTALGQVQSTYVGYYSLKHEHSGVWELQETAQRFELGGRQTAALVGQSRALRWLAEEVGHRWLQERIASLNRYAAELLSEVPGVKILTPQPGASGLLSFTFARAEPEAVVRRLAEEHNVLIRSIHERQALRLSTGFYNTEEELERVAAILRSWP。
  6. 6. use of S- (6-hexanol) -L-cysteine sulfoxide or cysteine sulfoxide lyase according to claim 5 for the preparation of a medicament or a composition for the control of dental caries, characterized in that: the cysteine sulfoxide lyase is a bacterial source cysteine sulfoxide lyase and is obtained by heterologous expression of pichia pastoris.
  7. Use of S- (6-hexanol) -L-cysteine sulfoxide for the preparation of a product for the prevention and treatment of dental caries, characterized in that: the S- (6-hexanol) -L-cysteine sulfoxide is compounded into milk tablets, and the milk tablets are prepared from S- (6-hexanol) -L-cysteine sulfoxide, pichia pastoris heterologous expression bacterial cysteine sulfoxide lyase spray-dried enzyme powder, milk powder and xylitol.
  8. 8. Use of S- (6-hexanol) -L-cysteine sulfoxide, according to claim 7, for the preparation of a product for the prevention and treatment of dental caries, characterized in that: s- (6-hexanol) -L-cysteine sulfoxide: the weight ratio of the cysteine sulfoxide lyase dry enzyme powder is (1: 1) - (1: 5), and each milk tablet contains 0.1-1 mg of S- (6-hexanol) -L-cysteine sulfoxide.
  9. 9. Use of S- (6-hexanol) -L-cysteine sulfoxide, according to claim 7, for the preparation of a product for the prevention and treatment of dental caries, characterized in that: the mass ratio of the milk powder to the xylitol is 20: 1, each milk tablet contains 2-5 g of milk powder.
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101696407A (en) * 2009-10-30 2010-04-21 北京工商大学 Chitosan-immobilized allinase and method for preparing allantolin allicin
CN104140384A (en) * 2014-07-15 2014-11-12 江南大学 Method for preparing thioalkyl/alkenyl cysteine sulfoxide by fractional crystallization

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101696407A (en) * 2009-10-30 2010-04-21 北京工商大学 Chitosan-immobilized allinase and method for preparing allantolin allicin
CN104140384A (en) * 2014-07-15 2014-11-12 江南大学 Method for preparing thioalkyl/alkenyl cysteine sulfoxide by fractional crystallization

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