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

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 ...

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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 binding as a polypeptide, the molecular weight of the polypeptide will be somewhat larger than that of drug design, and it will encounter many limitations when used in vivo experiments, such as difficulty in ensuring cell growth. Stability in the environment, and difficulty crossing the cell membrane to be absorbed by the cell, etc.

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