Synthesis method of liquid-phase segment of snake-venom-like tripeptide

A synthesis method and snake venom technology are applied in the field of liquid phase synthesis of short peptides, which can solve the problems of low cost, complicated synthesis process and high cost, and achieve the effects of low synthesis cost and simple and convenient method.

Inactive Publication Date: 2018-03-30
SHAANXI HUIKANG BIO TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] At present, most of the conventional methods for synthesizing snake venom-like tripeptides adopt the method of combining solid phase and liquid phase, that is, the fragment Boc-β-Ala-Pro-DAB(Boc)-OH or Fmoc- β-Ala-Pro-DAB(Boc)-OH, then synthesize Boc from the fragment Boc-β-Ala-Pro-DAB(Boc)-OH or Fmoc-β-Ala-Pro-DAB(Boc)-OH and benzylamine -β-Ala-P

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] (1) Synthesis of H-Pro-DAB(Boc)-NH-Bzl

[0023] ① Weigh 16.87g (0.05mol) Fmoc-Pro-OH and 6.33g (0.055mol) N-hydroxysuccinimide in a container, add 230mL tetrahydrofuran and stir to dissolve, then add 11.35g (0.055mol) N,N' -Dicyclohexylcarboimide, stirred at room temperature for 3 hours, and filtered to remove the precipitate to obtain a tetrahydrofuran solution of Fmoc-Pro-OSu.

[0024] ② Add 12.00g (0.055mol) H-DAB(Boc)-OH into 120mL tetrahydrofuran, then add 16.5mL (0.10mol) N,N-diisopropylethylamine, stir and dissolve, then add it to step ① In the tetrahydrofuran solution of Fmoc-Pro-OSu, stir the reaction at room temperature for 1.5 hours, concentrate by rotary evaporation at 30-40°C, add 350mL ethyl acetate to the concentrated solution, wash the organic phase with 0.5% hydrochloric acid for 3 times, anhydrous Dry over sodium sulfate, concentrate by rotary evaporation at 30-40°C, precipitate with ether, filter with suction, and dry to obtain 21.86 g of Fmoc-Pro-DA...

Embodiment 2

[0032]In ① of step (1) of this embodiment, the molar ratio of Fmoc-Pro-OH, N-hydroxysuccinimide, and N,N'-dicyclohexylcarboimide is 1:1.2:1.2, step (1 ) in ②, the molar ratio of Fmoc-Pro-OH, H-DAB(Boc)-OH, N,N-diisopropylethylamine is 1:1.2:2.5, step (1) in ③, Fmoc- The molar ratio of Pro-DAB(Boc)-OH, benzylamine, 1-hydroxybenzotriazole and N,N'-diisopropylcarboimide is 1:3:3:3, in step (2) , the molar ratio of H-Pro-DAB(Boc)-NH-Bzl, Boc-β-Ala-OH, 1-hydroxybenzotriazole, N,N'-diisopropylcarboimide is 1:1.3 :3:3, the other steps were the same as in Example 1 to obtain 5.35g of H-β-Ala-Pro-DAB-NH-Bzl with a purity of 96.7%, i.e. snake venom-like tripeptide, with a yield of 47.98%.

Embodiment 3

[0034] In ① of step (1) of this embodiment, the molar ratio of Fmoc-Pro-OH, N-hydroxysuccinimide, and N,N'-dicyclohexylcarboimide is 1:1:1, and step (1 ) in ②, the molar ratio of Fmoc-Pro-OH, H-DAB(Boc)-OH, N,N-diisopropylethylamine is 1:1:1.5, step (1) in ③, Fmoc- The molar ratio of Pro-DAB(Boc)-OH, benzylamine, 1-hydroxybenzotriazole and N,N'-diisopropylcarboimide is 1:1.5:1.5:1.5, in step (2) , the molar ratio of H-Pro-DAB(Boc)-NH-Bzl, Boc-β-Ala-OH, 1-hydroxybenzotriazole, N,N'-diisopropylcarboimide is 1:1.1 :1.5:1.5, other steps are the same as in Example 1, obtain 5.79g of H-β-Ala-Pro-DAB-NH-Bzl with a purity of 97.3%, i.e. snake venom-like tripeptide, yield 51.92%.

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Abstract

The invention discloses a synthesis method of a liquid-phase segment of a snake-venom-like tripeptide. The synthesis method comprises the following steps of adopting Fmoc-Pro-OH, H-DAB(Boc)-OH and benzylamine with low cost as raw materials to synthesize a protective segment H-Pro-DAB(Boc)-NH-Bzl firstly, then using Boc-beta-Ala-OH and H-Pro-DAB(Boc)-NH-Bzl to synthesize Boc-beta-Ala-Pro-DAB(Boc)-NH-Bzl, and after trifluoroacetic acid is adopted to carry out protecting-group removal on the Boc-beta-Ala-Pro-DAB(Boc)-NH-Bzl, separating, purifying and freeze-drying to obtain H-beta-Ala-Pro-DAB-NH-Bzl with the purity being greater than 95%, namely the snake-venom-like tripeptide. The synthesis method disclosed by the invention is simple and easy to implement and is low in cost; a synthesis method of the liquid-phase segment, with simple process and lower cost, is provided for synthesizing the snake-venom-like tripeptide.

Description

technical field [0001] The invention belongs to the technical field of cosmetics, and in particular relates to a liquid phase synthesis method of short peptides in polypeptides. Background technique [0002] Snake venom-like tripeptide (H-β-Ala-Pro-DAB-NH-Bzl) is a small peptide that mimics the activity of snake venom Waglerin I, which was found in the venom of Temple Viper (Tripidolaemus wagleri) and is the muscle nicotine Acetylcholine receptor (nmAChR) antagonists. H-β-Ala-Pro-DAB-NH-Bzl is a small molecule tripeptide synthesized by PENTAPHARM, a wholly-owned subsidiary of DSM Royal DSM Group, through high-tech biochemical technology, imitating fragments of effective molecular proteins (Waglerin1). The structure is similar to snake serum, but it is safer and more effective than botulinum toxin, so it can be safely applied to cosmetics, and has excellent smooth skin and rapid wrinkle removal properties. [0003] At present, most of the conventional methods for synthesizi...

Claims

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Application Information

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IPC IPC(8): C07K5/083C07K1/06C07K1/02
CPCC07K5/0806Y02P20/55
Inventor 张忠旗李乾李晨王慧王斌张佳旭杨小琳赵金礼
Owner SHAANXI HUIKANG BIO TECH CO LTD
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