Metastatic tumor deletion protein small-molecule cyclopeptide inhibitor as well as preparation method and application thereof

A technology for metastatic tumors and small molecules, applied in the field of biochemistry, can solve the problems of short peptides that are difficult to obtain inhibitory effects, difficult to ensure stability, and large molecular weight of peptides

Inactive Publication Date: 2013-10-02
SOUTHEAST UNIV
View PDF3 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it is difficult for short peptides to obtain ideal inhibitory effects, because short amino acid sequences are difficult to form an active ideal conformation in aqueous solution [Scholtz, J.M.; Baldwin, R.L. (1992) Annu Rev Bioph Biom21, 95-118.]
If the amino acid residues at the interface are used as a whole for competitive

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 more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Metastatic tumor deletion protein small-molecule cyclopeptide inhibitor as well as preparation method and application thereof
  • Metastatic tumor deletion protein small-molecule cyclopeptide inhibitor as well as preparation method and application thereof
  • Metastatic tumor deletion protein small-molecule cyclopeptide inhibitor as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1H2

[0100] Example 1H 2 Preparation of N-cyclo(Asp-Ala-Phe-Gln-Lys)-Val-OH

[0101] 0.8g of Fmoc-Val-OBzl- The resin was soaked in 10ml of anhydrous DMF and stirred at room temperature for 30min. Afterwards, use 25% Pip in DMF to mix with the resin for 20 min to remove the Fmoc protecting group.

[0102] Use DMF to wash the resin, then add 3ml of 3.8g Fmoc-Lys(Boc)-OH in DMF, 3ml of 0.3mol / L DCC in DMF and 3ml of 0.4mol / L HOBt in DMF, stir at room temperature for 15min, and perform coupling reaction.

[0103] After the reaction finishes, use DMF to wash the resin, and use the DMF solution of 25%Pip to mix with the resin for 20min, to remove the Fmoc protecting group, then wash with DMF to obtain Fmoc-Lys(Boc)-Val-OBzl- Prepare for the next coupling reaction.

[0104]Use Fmoc-Gln-OH, Fmoc-Phe-OH, Fmoc-Ala-OH and Fmoc-Asp(OtBu)-OH cycles to carry out chain reaction until Fmoc-Asp(OtBu)-Ala-Phe-Gln-Lys is obtained (Boc)-Val-OBzl-

[0105] Use 0.1N HBr / HOAc to treat for 1 h...

Embodiment 2H2

[0107] Example 2H 2 Preparation of N-cyclo(Lys-Lys-Val-Ala-Asp)-Met-Ala-OH.

[0108] 1 mmol of Fmoc-Ala-OBzl- The resin was soaked in 10ml of anhydrous DMF and stirred at room temperature for 30min. Afterwards, use 10% Pip in DMF to mix with the resin for 30 min to remove the Fmoc protecting group.

[0109] Wash the resin with DMF, then add a DMF solution containing 2 mmol Fmoc-Met(Boc)-OH, 5 ml 0.3 mol / L DCC in DMF and 5 ml 0.4 mol / L HOBt in DMF, and stir at room temperature for 10 min to carry out the coupling reaction.

[0110] After the reaction, use DMF to wash the resin, and use the DMF solution of 3ml of 10%Pip to mix with the resin for 30min to remove the Fmoc protecting group, and then wash with DMF to obtain Fmoc-Met(Boc)-Ala-OBzl- , ready for the next coupling reaction.

[0111] Use Fmoc-Asp-OH, Fmoc-Ala-OH, Fmoc-Val-OH, Fmoc-Lys-OH and Fmoc-Lys(OtBu)-OH in sequence for chain coupling reaction until Fmoc-Lys(OtBu)-Lys is obtained -Val-Ala-Asp-Met-Ala--

[...

Embodiment 3

[0114] Example 3H 2 Preparation of N-cyclo(Lys-Ile-Gly-Ser-Asp)-Leu-OH.

[0115] 1 mmol of Fmoc-Leu-OBzl- The resin was soaked in 10ml of anhydrous DMF and stirred at room temperature for 30min. After that, use 30% Pip in DMF solution to mix with the resin for 10 min to remove the Fmoc protecting group.

[0116] Wash the resin with DMF, then add a DMF solution containing 3 mmol Fmoc-Asp(Boc)-OH, 5 ml 0.5 mol / L DCC in DMF and 5 ml 0.6 mol / L HOBt in DMF, and stir at room temperature for 20 min to carry out the coupling reaction.

[0117] After the reaction, use DMF to wash the resin, and use the DMF solution of 1ml of 30%Pip to mix with the resin for 10min to remove the Fmoc protecting group, and then wash with DMF to obtain Fmoc-Met(Boc)-Ala-OBzl- Prepare for the next coupling reaction.

[0118] Use Fmoc-Ser-OH, Fmoc-Gly-OH, Fmoc-Ile-OH, Fmoc-Lys-OH cycle to carry out chain reaction until Fmoc-Lys(OtBu)-Ile-Gly-Ser-Asp-

[0119] Use 0.12N HBr / HOAc to treat for 0.5h to ...

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

No PUM Login to view more

Abstract

The invention provides metastatic tumor deletion protein small-molecule cyclopeptide, derivatives or salts thereof, a preparation method for the metastatic tumor deletion protein small-molecule cyclopeptide, the derivatives or salts thereof and an application of the metastatic tumor deletion protein small-molecule cyclopeptide, the derivatives or salts thereof in preparation of antitumor medicaments. The metastatic tumor deletion protein small-molecule cyclopeptide is low in molecular weight, high in stability and very low in toxicity and can enter cells through cell membranes to inhibit endocytosis of tumor cells and interfere morphologic change of the cell membranes and conduction of relevant antitumor signals by inhibiting dimerization of Mtss1 protein, so that cell proliferation and growth caused by tumor stimulating factors such as epidermal growth factors EGF, platelet derived growth factor PDGF or sonic hedgehog (shh) factors are weakened, wherein the in-vitro inhibition activity of nanomole-scale inhibitor-protein can remarkably inhibit the endocytosis of the cells after the inhibitor-protein is directly added into cell culture fluid without being transfected or packaged by lipidosome.

Description

technical field [0001] The invention belongs to the field of biochemistry, and in particular relates to a small-molecule cyclic peptide inhibitor of metastatic tumor deletion protein, and also relates to a preparation method and application of the metastatic tumor deletion protein small-molecule cyclic peptide compound. Background technique [0002] Proteins are the key functional building blocks that determine the survival, aging, disease and death of organisms. However, the application of proteins in medicine, scientific research and industrial processes is limited by their complexity, high cost, poor chemical stability and low bioavailability. This requires new chemical techniques to obtain simpler, smaller, cheaper, more stable and biocompatible molecules that can selectively, specifically and accurately complete the functions of proteins. In the synthesis process, if the molecular conformation can be accurately simulated as the smallest building block of protein (such ...

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
no application Login to view more
IPC IPC(8): C07K7/56C07K1/06C07K1/04A61K38/12A61P35/00
Inventor 吉民曹萌詹熙顾宁
Owner SOUTHEAST UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap