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Preparation process of RGD cyclized pentapeptide

A preparation process and intermediate technology, applied in the field of solid-phase peptide synthesis, can solve the problems of heavy metal palladium and high price in drugs, and achieve the effects of easy industrial production, simple price operation, and high yield

Pending Publication Date: 2020-01-10
南京恒远科技开发有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The Asp protection amino acid used in this technology, protecting group is Oall, and price is higher, and sloughs off Oall in addition, needs to use expensive tetrakis (triphenylphosphine) palladium, and the use of tetrakis (triphenylphosphine) palladium in addition gives Drugs bring hidden dangers of residual heavy metal palladium

Method used

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  • Preparation process of RGD cyclized pentapeptide
  • Preparation process of RGD cyclized pentapeptide
  • Preparation process of RGD cyclized pentapeptide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] Example 1: Preparation of Cyclic [Aspartyl-Glycyl-Arginyl (Pbf)-Lysyl (Dde)-D-Phenylalanyl]

[0017] Follow the steps below:

[0018] 1. Preparation of Intermediate 5

[0019] name molecular weight Proportion Feed amount (g) CTC resin (Sub1.00mmol / g) / 1.0 10.00 Fmoc-Asp(Ome) 369.37 3.0 11.08 DIEA 129.24 12.0 15.51

[0020] Weigh 10.00g 10.00mmol (W gram) (Nmmol) of 2-Chlorotrityl chloride resin resin, add the resin into the reactor, add DMF to fully wash and swell the resin.

[0021] Based on the molar weight N of 2-Chlorotrityl chloride resin resin, weigh the following materials according to a certain feeding ratio: Fmoc-Asp-OMe11.08g (3.0 times the amount), dissolve it with an appropriate amount of DMF, add it to the reactor, and add DIEA15.51g (12.0 times the amount), the coupling reaction is 2.0±0.5 hours, and the DMF is washed 3 times. Block with DCM / MeOH / DIEA (3:1:1) for 10 minutes, repeat once. Methanol shrinks, and...

Embodiment 2

[0039] Example 2: Preparation of Cyclic [Aspartyl-Glycyl-Arginyl (Pbf)-Lysyl (Dde)-D-Phenylalanyl]

[0040]Follow the steps below:

[0041] 1. Preparation of Intermediate 5

[0042] name molecular weight Proportion Feed amount (g) CTC resin (Sub1.00mmol / g) / 1.0 10.00 Fmoc-Asp(Oall) 395.40 3.00 11.86 DIEA 129.24 12.0 15.51

[0043] Weigh 10.00g 10.00mmol (W gram) (Nmmol) of 2-Chlorotrityl chloride resin resin, add the resin into the reactor, add DMF to fully wash and swell the resin.

[0044] Based on the molar weight N of 2-Chlorotrityl chloride resin resin, weigh the following materials according to a certain feeding ratio: Fmoc-Asp-Oall 11.86g (3.0 times the amount), dissolve it with an appropriate amount of DMF, add it to the reactor, and add DIEA15.51g (12.0 times the amount), the coupling reaction is 2.0±0.5 hours, and the DMF is washed 3 times. Block with DCM / MeOH / DIEA (3:1:1) for 10 minutes, repeat once. Methanol shrinks, ...

Embodiment 3

[0063] Example 3: Preparation of Cyclic [Aspartyl-Glycyl-Arginyl (Pbf)-Lysyl (Boc)-D-Phenylalanyl]

[0064] Follow the steps below:

[0065] 1. Preparation of Intermediate 5

[0066] name molecular weight Proportion Feed amount (g) CTC resin (Sub1.00mmol / g) / 1.0 10.00 Fmoc-Asp(Oall) 395.40 3.00 11.86 DIEA 129.24 12.0 15.51

[0067] Weigh 10.00g 10.00mmol (W gram) (Nmmol) of 2-Chlorotrityl chloride resin resin, add the resin into the reactor, add DMF to fully wash and swell the resin.

[0068] Based on the molar weight N of 2-Chlorotrityl chloride resin resin, weigh the following materials according to a certain feeding ratio: Fmoc-Asp-Oall 11.86g (3.0 times the amount), dissolve it with an appropriate amount of DMF, add it to the reactor, and add DIEA15.51g (12.0 times the amount), the coupling reaction is 2.0±0.5 hours, and the DMF is washed 3 times. Block with DCM / MeOH / DIEA (3:1:1) for 10 minutes, repeat once. Methanol shrinks,...

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Abstract

The invention provides a preparation process of RGD cyclized pentapeptide. Aiming at the special structure of the cyclic peptide, the process comprises the following steps: immobilizing carboxyl of anaspartic acid side chain on resin; after amino acid coupling is finished, respectively removing a protecting group (OMe or Oall) of carboxyl of a aspartic acid main chain and an Fmoc group on D-phenylalanine; and then carrying out solid-phase cyclization, and cutting the resin after the cyclization is finished so as to obtain the annular RGD pentapeptide with high purity and high yield. The process is low in cost, simple to operate and easy for industrial production.

Description

technical field [0001] The invention relates to the field of solid-phase polypeptide synthesis, in particular to a preparation process of RGD cyclized pentapeptide. Background technique [0002] With the change of environmental factors, the morbidity and mortality of various cancers have increased. In some tumor cells or endothelial cells of tumor neovascularization, certain integrin receptors such as αvβ3 are often highly specifically expressed, while the content in blood vessels of normal tissues is very small. RGD peptides are short peptides containing arginine, glycine, and aspartic acid (Arg-Gly-Asp), which serve as recognition sites for the interaction between integrins and their ligands, and can be specifically expressed with tumor cells or new blood vessels Certain integrins such as αvβ3 bind. Therefore, such receptors can be used as targets for tumor-targeted therapy, and the use of exogenous RGD peptides to compete for binding to integrin receptors can target mar...

Claims

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Application Information

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IPC IPC(8): C07K7/64C07K1/06C07K1/04
CPCC07K7/64Y02P20/55
Inventor 胡峻计炜徐春夏徐佩
Owner 南京恒远科技开发有限公司