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RGD polypeptide-camptothecin polypeptide drug conjugate and application thereof

A technology of drug conjugates and camptothecin, which is applied in the direction of drug combinations, antineoplastic drugs, and pharmaceutical formulations, can solve the problems of limiting camptothecin, achieve the effects of reducing biological toxicity, reducing accumulation, and improving antitumor efficacy

Pending Publication Date: 2020-04-28
YUNNAN MINZU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Camptothecin has excellent anticancer activity as a plant drug, but its stability, solubility, and toxic and side effects severely limit the clinical use of camptothecin. How to reduce the toxic and side effects of camptothecin

Method used

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  • RGD polypeptide-camptothecin polypeptide drug conjugate and application thereof
  • RGD polypeptide-camptothecin polypeptide drug conjugate and application thereof
  • RGD polypeptide-camptothecin polypeptide drug conjugate and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] The preparation method of a RGD polypeptide-camptothecin-based polypeptide drug conjugate provided in this embodiment includes the following contents:

[0051] (1) Modification of camptothecin:

[0052] Using camptothecin and succinic acid dry as raw materials, DCM dehydrated as solvent, adding DBU to react at 10°C, after 4 hours, the reaction was completed, purified by methanol recrystallization to obtain camptothecin 20-OH modified product.

[0053] (2) Preparation of peptide drug conjugates of peptide-camptothecin

[0054](a) Rink amide resin was used as the starting material, soaked in DCM for 30 minutes, and then deprotected with piperidine / DMF; the ratio of Rink amide resin to DCM was 2:5.

[0055] (b) Dissolve Fmoc-Asp(OTBu)-OH and HBTU in DMF, connect with resin, and add DIEA to react; wherein the proportion of Fmoc-Asp(OTBu)-OH, HBTU, DMF is 1: 1:4, where DIEA is sufficient;

[0056] (c) Use piperidine / DMF to deprotect after the reaction;

[0057] (d) Fmoc...

Embodiment 2

[0061] The preparation method of a RGD polypeptide-camptothecin-based polypeptide drug conjugate provided in this embodiment includes the following contents:

[0062] (1) Modification of camptothecin:

[0063] Use camptothecin and succinic acid dry as raw materials, DCM with water removed as solvent, add DBU to react at 15°C, after 4 hours the reaction ends, purify with methanol recrystallization, and obtain camptothecin 20-OH modified product.

[0064] (2) Preparation of peptide drug conjugates of peptide-camptothecin

[0065] (a) Use Rink amide resin as the starting material, soak in DCM for 30 minutes, and then remove the protection with piperidine / DMF;

[0066] (b) Dissolving Fmoc-Asp(OTBu)-OH and HBTU in DMF, connecting with resin, and adding DIEA for reaction;

[0067] (c) Use piperidine / DMF to deprotect after the reaction;

[0068] (d) Fmoc-Gly-OH and Fmoc-Arg(pdf)-OH are connected according to the methods in (b) and (c) above;

[0069] (e) After the required amino...

Embodiment 3

[0075] The preparation method of a RGD polypeptide-camptothecin-based polypeptide drug conjugate provided in this embodiment includes the following contents:

[0076] (1) Modification of camptothecin:

[0077] Camptothecin and succinic acid were used as raw materials, DCM dehydrated as solvent, DBU was added to react at 0°C to room temperature, the reaction was completed after 4 hours, and purification was carried out by methanol recrystallization. The modified product of camptothecin 20-OH was obtained.

[0078] (2) Preparation of peptide drug conjugates of peptide-camptothecin

[0079] (a) Use Rink amide resin as the starting material, soak in DCM for 30 minutes, and then remove the protection with piperidine / DMF;

[0080] (b) Dissolving Fmoc-Asp(OTBu)-OH and HBTU in DMF, connecting with resin, and adding DIEA for reaction;

[0081] (c) Use piperidine / DMF to deprotect after the reaction;

[0082] (d) Fmoc-Gly-OH and Fmoc-Arg(pdf)-OH are connected according to the methods...

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Abstract

The invention discloses a camptothecin and Arg-Gly-Asp (RGD) polypeptide conjugate as well as a preparation method and application thereof. The structure of the polypeptide coupled camptothecin drug includes the following three parts: A, an RGD targeting peptide; B, a linker; and C, anticancer drug camptothecin, wherein the RGD polypeptide and the camptothecin are connected by using succinic anhydride as a connecting arm; and the synthesized RGD-camptothecin polypeptide drug conjugate can deliver the camptothecin to tumor cells, tissue, tumor microenvironment and other tumor sites to achieve the purpose of improving the problem of solubility of the camptothecin, making the drug camptothecin have a targeted effect, reducing the toxic and side effects on normal cells and tissue, so as to achieve the specific anti-tumor purpose.

Description

technical field [0001] The invention belongs to the technical field of polypeptide drugs, and specifically relates to a polypeptide drug conjugate based on RGD polypeptide-camptothecin, a preparation method and an application thereof. Background technique [0002] As the number one killer in the world, tumor is threatening the lives of more and more people. According to the data released by the Ministry of Health of my country, whether in urban or rural areas, nausea and tumors have surpassed cardiovascular diseases to become the number one cause of death among Chinese residents. [0003] In recent decades, with the development of medical and health care, excellent progress has been made in various aspects of cancer treatment and control, and various drugs and treatment methods are emerging, but surgery, chemotherapy and radiotherapy are still the most important. However, it is still difficult for these treatment methods to have a good effect on patients. Although ordinary ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/64A61K31/4745A61P35/00
CPCA61K31/4745A61K47/64A61P35/00
Inventor 樊保敏郝朝威吴疆六兆祥黄韬林成源
Owner YUNNAN MINZU UNIV
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