A liver cancer targeting ruthenium complex and its preparation method and application
A ruthenium complex, liver cancer technology, applied in the field of medicine, can solve problems such as lack of tumor targeting, achieve good anti-cancer effect, improve water solubility, and good biocompatibility.
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[0040] The present invention also provides a preferred embodiment of the preparation method of the aforementioned liver cancer-targeted ruthenium complex, the preparation process is as follows: figure 1 shown, including:
[0041] Step A, synthetic peptide
[0042] Step B, connecting β-alanine to the N-terminus of the polypeptide to obtain
[0043] Step C, adding the carboxyl-containing ruthenium complex and the product obtained in step B to the reactive agent for reaction, and purifying the product to obtain
[0044] The present invention selects a ruthenium complex (Ru) with an active carboxyl structure (-COOH) and a polypeptide with liver cancer targeting, and designs between the two, which can improve the water-soluble β-alanine of the product, and finally synthesizes a protein with liver cancer targeting Oriented ruthenium complexes (Ru-T-Pep).
[0045] In the present invention, the polypeptide can be of any structure type, and a preferred polypeptide is HCBP1 (se...
Embodiment 1
[0053] Embodiment 1 (reaction process is as figure 2 shown)
[0054] (1) Solid-phase synthesis of polypeptides is prepared by Rink-Amide-MBHA-Resin resin (10eq, degree of substitution: 0.53mmol / L). Nitrogen gas is passed through at room temperature, and the reaction is carried out by bubbling. The amino acids with Fmoc protection are sequenced FQHPSFI sequential synthesis of peptides.
[0055] (2) Using HCTU (1eq) and DIPEA (0.5eq) as a coupling agent, link the β-Ala amino acid to the N-terminus of the above polypeptide to obtain FQHPSFI-β-A-NH 2 , mass confirmed that the target product with m / z 473.5 was obtained.
[0056](3) Condensation reaction The product of step (2) is mixed with ruthenium complex (1.2eq), HoBt (3eq), PyBop (3eq) and DIPEA (3eq), and the reaction is carried out under nitrogen for 10 hours. In the ruthenium complex The carboxyl group of β-alanine undergoes a coupling condensation reaction with the amino group in β-alanine. The above crude product was...
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