A kind of in situ self-assembled polypeptide derivatives in response to pathological microenvironment and its application
A technology of peptide derivatives and microenvironment, applied in the field of biomedicine, can solve problems such as the non-universality of tumor cells, long-term toxicity of nanomaterials, drug leakage, etc., achieve strong cancer cell killing effect, enhance retention, and reduce toxic and side effects Effect
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1 2
[0050] Example 1 Synthesis of disulfide linker Fmoc-CS (compound of formula II)
[0051] In a 250mL round-bottom flask, add cystamine dihydrochloride (2.25g, 10mmol), NaHCO 3 (2.52 g, 30 mmol), 1,4-dioxane (35 mL), and an appropriate amount of water (50 mL), and then added with magnetic stirring, after the solution became clear, added succinic anhydride (1 g, 10 mmol), and stirred overnight.
[0052] Continue adding NaHCO to the round bottom flask 3 (840 mg), a mixed solution of Fmoc-OSu (3.37 g, 10 mmol) and acetone (25 mL) was added dropwise, and stirring was continued overnight.
[0053] Use a high-speed centrifuge to centrifuge (10000rpm, 5min) to collect the supernatant, remove the organic solvent by rotary evaporation, then add about 200mL of water to mix, and then adjust the pH to 2-3 with 1M HCl, a white product is precipitated, and the white solid is collected by filtration , freeze-dried using a freeze dryer, and the result is the product.
Embodiment 2
[0054] Example 2 Polypeptide derivative Nap- with side chain protected disulfide bond D F D Synthesis of FY-CS-DEVD(tBu) (the compound of formula III)
[0055] Weigh 0.5 g of dichloro resin into a solid-phase synthesis tube, add about 10 mL of dichloromethane (DCM), place the solid-phase synthesis tube on a shaking table to swell for 5 minutes, and squeeze out the solvent in the tube with an ear-washing ball. Weigh 0.5 mmol of the first amino acid Fmoc-Asp(OtBu)-OH into a 20 mL vial, add about 10 mL of DCM, and then add 1 mmol (200 μL) DIEA, pipette with a plastic dropper to dissolve it completely, and then add it to the solution. In a solid-phase synthesis tube, the reaction was carried out at room temperature for 2 h. After the reaction, the reaction solution was extruded, washed twice with DCM and three times with N,N-dimethylformamide (DMF), and about 10 mL of freshly prepared methanol solution (DCM:CH) was added. 3 OH:DIEA=17:2:1), to block the unreacted active chlorin...
Embodiment 3
[0056] Example 3 Synthesis of BSO (compound of formula IV) whose amino group is protected by Fmoc
[0057] In a 100 mL eggplant flask, add butthionine sulfoximine (1.11 g, 5 mmol) and NaHCO 3 (840 mg, 10 mmol), dissolved in an appropriate amount of water, and cooled to 0°C. Fmoc-OSu (1.69 g, 5 mmol) was dissolved in 1,4-dioxane (20 mL), added dropwise to the above system, reacted in ice bath for 1 h, and then reacted at room temperature for 3 h. After the reaction was completed, poured into 200 mL of water, extracted twice with ether, adjusted the pH to about 2 with 1M HCl, extracted three times with ethyl acetate, evaporated to remove the solvent, and lyophilized.
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More