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CN-122011131-A - Polypeptide or derivative thereof based on artificial intelligence design, pharmaceutically acceptable salt and application thereof

CN122011131ACN 122011131 ACN122011131 ACN 122011131ACN-122011131-A

Abstract

The invention relates to the technical field of biological pharmacy, and in particular provides a polypeptide or a derivative, pharmaceutically acceptable salt and application thereof based on artificial intelligence design, wherein the amino acid sequence of the polypeptide is shown as SEQ ID NO. 1. The polypeptide or the derivative and the pharmaceutically acceptable salt thereof can be combined with PD-1 and CTLA-4 at the same time, can effectively block the combination between PD-1 and CTLA-4 and the ligand thereof, relieve the inhibition effect of immune checkpoint proteins PD-1 and CTLA-4 on immune cells, and remarkably enhance the anti-tumor immune response of organisms. The polypeptide or the derivative and the pharmaceutically acceptable salt thereof can be used for detecting PD-1 and/or CTLA-4 and can also be used for treating or preventing related diseases caused by PD-1 and/or CTLA-4.

Inventors

  • HE BING
  • Lv Tianxu
  • YAO JIANHUA

Assignees

  • 腾讯科技（深圳）有限公司

Dates

Publication Date
20260512
Application Date
20260414

Claims (13)

  1. 1. A polypeptide or a derivative and pharmaceutically acceptable salt thereof is characterized in that the amino acid sequence of the polypeptide is shown as SEQ ID NO. 1.
  2. 2. A nucleic acid molecule encoding the polypeptide of claim 1 or a derivative, pharmaceutically acceptable salt thereof.
  3. 3. An expression vector comprising the nucleic acid molecule of claim 2.
  4. 4. A recombinant cell comprising the nucleic acid molecule of claim 2 or the expression vector of claim 3, or expressing the polypeptide of claim 1 or a derivative, pharmaceutically acceptable salt thereof.
  5. 5. A conjugate comprising the polypeptide of claim 1 or a derivative thereof, a pharmaceutically acceptable salt, and a coupling moiety coupled thereto, wherein the coupling moiety is selected from a purification tag or label.
  6. 6. Use of the polypeptide of claim 1 or a derivative thereof, a pharmaceutically acceptable salt thereof, the nucleic acid molecule of claim 2, the expression vector of claim 3 or the recombinant cell of claim 4 in the preparation of a medicament which is an inhibitor of both PD-1 and CTLA-4 targets.
  7. 7. Use of the polypeptide of claim 1 or a derivative thereof, a pharmaceutically acceptable salt thereof, the nucleic acid molecule of claim 2, the expression vector of claim 3 or the recombinant cell of claim 4 in the manufacture of a medicament for the treatment or prevention of a disease associated with PD-1 and/or CTLA-4.
  8. 8. The use according to claim 7, wherein the PD-1 and/or CTLA-4 associated disease comprises a tumor or cancer.
  9. 9. The use of claim 8, wherein the tumor or cancer comprises a solid tumor or a hematological tumor.
  10. 10. Use of the polypeptide of claim 1 or a derivative, pharmaceutically acceptable salt thereof, or conjugate of claim 5 in the preparation of a reagent or kit for detecting PD-1 and/or CTLA-4.
  11. 11. A medicament comprising the polypeptide of claim 1 or a derivative thereof, a pharmaceutically acceptable salt thereof, the nucleic acid molecule of claim 2, the expression vector of claim 3, or the recombinant cell of claim 4.
  12. 12. A reagent or kit comprising the polypeptide of claim 1 or a derivative thereof, a pharmaceutically acceptable salt or the conjugate of claim 5.
  13. 13. A method of detecting PD-1 and/or CTLA-4, comprising: contacting a sample to be tested with the polypeptide of claim 1 or a derivative, pharmaceutically acceptable salt, conjugate of claim 5, or the reagent or kit of claim 12; determining whether PD-1 and/or CTLA-4 is contained in the sample to be tested based on the signal generated by the contacted product.

Description

Polypeptide or derivative thereof based on artificial intelligence design, pharmaceutically acceptable salt and application thereof Technical Field The invention belongs to the technical field of biological pharmacy, and particularly relates to polypeptide or a derivative, pharmaceutically acceptable salt and application thereof based on artificial intelligence design. Background Binding of PD-1 to its ligand PD-L1 can inhibit T cell activation and proliferation, thereby inducing immune tolerance. However, in tumor microenvironments, abnormal activation of this pathway leads to depletion of T cell function, allowing tumor cells to escape immunologically, which makes it a core target for tumor immunotherapy. CTLA-4 is another important cell membrane receptor that regulates the activation threshold of T cells mainly in the early stages of the immune response. Activation of CTLA-4 as a competitive antagonist of CD28 can block costimulatory signals, limiting initial expansion of T cells. Therefore, CTLA-4 is of great importance in regulating the intensity and breadth of anti-tumor immune responses. Currently, the main clinical scheme aiming at PD-1 and CTLA-4 targets is monoclonal antibodies (Monoclonal Antibodies, mAbs), and the interaction between the monoclonal antibodies and corresponding ligands is blocked through high binding of PD-1 or CTLA-4, so that the inhibition of T cells is relieved, and the recognition and killing capacity of an immune system on tumor cells are restored. Blocking the PD-1 pathway alone often results in compensatory escape of the tumor by activating CTLA-4 or other immune checkpoints, resulting in insufficient therapeutic resistance or immune stimulation. The combined blockade against PD-1 and CTLA-4 has been demonstrated clinically to significantly enhance the killing efficacy of the immune system against tumors by complementary mechanisms. In the field of polypeptide medicaments, the research on double-target peptides capable of simultaneously and accurately combining and blocking two targets of PD-1 and CTLA-4 is very few, and the design of the molecules requires very high spatial configuration accuracy and screening technology, so that the development of the technology for combining the binding affinity of the two targets and the stability of the molecules is relatively difficult. Therefore, a novel PD-1 and CTLA-4 double-target inhibition polypeptide is developed, and the polypeptide has important clinical value and application potential in the field of tumor immunotherapy. Disclosure of Invention The present invention aims to solve at least one of the technical problems existing in the prior art to at least some extent. Therefore, the invention provides a polypeptide or a derivative thereof, pharmaceutically acceptable salt and application thereof based on artificial intelligence design. In a first aspect of the invention, the invention provides a polypeptide or a derivative, pharmaceutically acceptable salt thereof. According to the embodiment of the invention, the amino acid sequence of the polypeptide is shown as SEQ ID NO. 1. The polypeptide or the derivative and the pharmaceutically acceptable salt thereof can be combined with PD-1 and CTLA-4 simultaneously, and can block the combination between PD-1 and CTLA-4 and the ligand thereof respectively, relieve the inhibition effect of immune checkpoint proteins PD-1 and CTLA-4 on immune cells and obviously enhance the immune response of organisms, thereby realizing the treatment of diseases. In addition, the polypeptide or the derivative thereof and the pharmaceutically acceptable salt thereof can be used for qualitatively and/or quantitatively detecting PD-1 and/or CTLA-4. In a second aspect of the invention, the invention provides a nucleic acid molecule. According to an embodiment of the invention, the nucleic acid molecule encodes a polypeptide as described previously or a derivative, pharmaceutically acceptable salt thereof. The polypeptide or the derivative and the pharmaceutically acceptable salt thereof coded by the nucleic acid molecule can be combined with PD-1 and CTLA-4 simultaneously, and simultaneously blocks the combination between the PD-1 and the CTLA-4 and the ligand thereof respectively, so that the inhibition effect of immune checkpoint proteins PD-1 and CTLA-4 on immune cells is relieved, the immune response of an organism is obviously enhanced, and the treatment of diseases is realized. In addition, the polypeptide or the derivative thereof and the pharmaceutically acceptable salt thereof can be used for qualitatively and/or quantitatively detecting PD-1 and/or CTLA-4. In a third aspect of the invention, the invention provides an expression vector. According to an embodiment of the invention, the expression vector carries the aforementioned nucleic acid molecule. Therefore, the expression of the polypeptide or the derivative and the pharmaceutically acceptable salt thereof is effectively realized, and th