Mini protein and its application

Abstract

The invention discloses a kind of mini protein and its application. The miniprotein uses the 3-alpha helical bundle of the albumin binding domain as a skeleton protein, and cationic amino acids are introduced into at least one of the three-dimensional structure surface, the N-terminal, and the C-terminal of the skeleton protein, and through the Cationic amino acids are at least connected to key amino acid sites where p53 binds to MDM2 / MDMX. The mini-protein of the present invention has the ability to enter cells and bind to albumin and MDM2 / MDMX, and can well inhibit the interaction between p53 and MDM2 / MDMX, and can be used for the preparation of anticancer drugs, etc., and can be used for large-scale production and application.

Description

technical field [0001] The invention relates to a class of mini-proteins, especially a mini-protein that can be used as an inhibitor of the interaction between MDM2 / MDMX and p53, and this type of mini-protein also has the ability to bind serum albumin. Background technique [0002] p53 is one of the most important human tumor suppressor genes, and the p53 protein produced by its expression is the executor of tumor suppressor function. p53 inhibits the proliferation of abnormal or potentially neoplastic cells by participating in the regulation of cell cycle arrest, cell differentiation and apoptosis. The occurrence and development of all tumors are accompanied by the inactivation or loss of p53, and the anti-tumor effect can be achieved by restoring the activity of p53. In addition to the inactivation of p53 protein caused by p53 gene deletion and mutation, there are still some tumors without p53 gene mutation, but due to the influence of negative regulatory proteins, the p5...

AI Technical Summary

Problems solved by technology

In 2013, Roche developed a α-helical short peptide dual inhibitor that uses cyclization to stabilize the structure, in order to solve the shortcomings of linear polypeptides that are easily degraded by enzymes and unstable in the physiological environment

However, in fact, the research on most p53-MDM2 / MDMX polypeptide inhibitors is very limited, mainly for two reasons: first, p53 and MDM2 / MDMX are located in cells, but the polypeptide itself does not have the ability to enter cells; Second, after entering the body, the circulation time of the inhibitor in the body is too short, and it is easily excreted by the kidneys, so it cannot exert its efficacy

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