Solid-phase synthesis method of NMDA receptor regulating agent tetrapeptide derivative
A peptide derivative, solid-phase synthesis technology, applied in the preparation methods of peptides, chemical instruments and methods, peptides, etc., can solve the problems of complex synthesis and purification processes, poor reactivity of amino and carboxyl groups, and unfavorable amplification production, and achieve high efficiency. Solid-phase synthesis, stable yield, and improved efficiency
Inactive Publication Date: 2018-06-12
SHENZHEN INST OF ADVANCED TECH
View PDF4 Cites 2 Cited by
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
[0005] In the prior art (US20130035292A1), tetrapeptide derivatives of NMDA receptor modulators are prepared by multi-step liquid-phase organic chemical reactions, in which multiple intermediates need to be separated by column chromatography, the synthesis and purification process is complicated, and the total yield low and takes a long time, which is not conducive to scale-up production
[0006] At present, the tetrapeptide derivatives of NMDA receptor modulators are prepared by a multi-step liquid phase method. Compared with the liquid phase method, the solid phase peptide synthesis method does not require cumbersome purification processes, and is more convenient and fast. However, due to the TPPT tetrapeptide derivatives The sequence contains two prolines, and the reactivity of the amino and carboxyl groups is poor, so it is difficult to use conventional solid-phase peptide synthesis reagents to efficiently synthesize amide compounds containing such prolines. Therefore, how to improve proline Reactivity of acid, developing a kind of efficient, fast solid-phase synthesis method for preparing TPPT tetrapeptide and its analogues, is the technical problem to be solved in the present invention
Method used
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View moreImage
Smart Image Click on the blue labels to locate them in the text.
Smart ImageViewing Examples
Examples
Experimental program
Comparison scheme
Effect test
Embodiment 1
[0050] Example 1 Preparation of NMDA receptor regulator tetrapeptide derivative NH 2 -Thr-Pro-BenylPro-Thr-CONH 2
[0051] Preparation of Fmoc-Thr-resin conjugates
[0052] In a 100mL solid phase reactor, add Rink Amide AM resin (0.56mmol / g, 7.5g, 4.2mmol) and CH 2 Cl 2 (40ml), swell the resin for 30min. Extract CH 2 Cl 2 ,spare.
[0053] The Fmoc protecting group of the resin was removed with 20% piperidine / DMF solution (40ml). After 10min, the resin was washed with DMF (4x 40mL) and then with anhydrous DMF (2x 40mL) for later use. At the same time, Fmoc-Thr(tBu)-OH (3.0eq) and HATU (3.0eq) were dissolved in anhydrous DMF (40ml), and DIEA (4.0eq) was added to the solution, and the reaction was completed for 5min, and the reaction solution was transferred to Into the resin for removal of Fmoc, N 2 Mix well by bubbling. Condensate for 0.5-1h (use ninhydrin reagent to detect the reaction is complete), remove the reaction solution, and wash the resin with DMF (4x 40mL). ...
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More PUM
Login to View More Abstract
The invention provides a solid-phase synthesis method of an NMDA receptor regulating agent tetrapeptide derivative. The solid-phase synthesis method comprises the following steps: (1) through condensation coupling and removal of amino protection groups, obtaining a Thr-solid-phase synthesis resin conjugate; (2) through triphosgene activated amino acids, carrying out condensation coupling to obtainBenzylPro-Thr-solid-phase synthesis resin; (3) through triphosgene activated amino acids, carrying out condensation coupling to obtain Pro-BenylPro-Thr-solid-phase synthesis resin, and after removingprotection groups and cracking the solid-phase synthesis resin, obtaining NH2-Thr-Pro-BenylPro-Thr-CONH2. The solidification synthesis method is adopted, and the activation of praline is carried outby using triphosgene, so that the condensation reaction efficiency is improved effectively.
Description
technical field [0001] The invention relates to the field of biopharmaceuticals, in particular to a preparation method of tetrapeptide derivatives. Background technique [0002] US20130035292A1 discloses a class of NMDA (N-methyl-D-astonin) receptor modulators and applications thereof. NMDA receptors are a subtype of ionotropic glutamate receptors, which are heteromers composed of multiple subunits, and are mainly distributed in the central nervous system. Evidence in recent years has shown that the subunits that make up NMDA receptors have complex physiological and pharmacological properties and participate in many important physiological functions of the nervous system. The NMDA receptor is not only related to cognitive function and pain perception, but its abnormality can also lead to the occurrence of various diseases such as Alzheimer's disease, Parkinson's disease, epilepsy, and cerebral ischemia. target. As a kind of NMDA receptor modulator, TPPT tetrapeptide can s...
Claims
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More Application Information
Patent Timeline
Login to View More IPC IPC(8): C07K5/103C07K1/06C07K1/04
CPCC07K5/101Y02P20/55
Inventor 粟武房丽晶潘正银武春雷
Owner SHENZHEN INST OF ADVANCED TECH