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An immune peptide and immune drug technology, applied in the field of biomedicine to achieve the effect of enhancing the body's immune response
Active Publication Date: 2021-06-22
NANKAI UNIV
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So far, there has been no relevant research on the use of a single drug that has the triple function of IDO1 inhibitor, PD
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Embodiment 1
[0083] Example 1 Synthesis of polypeptide indoximod-GFFY
[0084] It was synthesized by Fmoc-short peptide solid-phase synthesis method. The specific steps are:
[0085] 1) Weigh 0.5 mmol of 2-Cl-Trt resin in a solid-phase synthesizer, add 10 mL of anhydrous dichloromethane (DCM), place it on a shaking table and shake for 10 min to fully swell the 2-Cl-Trt resin;
[0086] 2) Use ear washing balls to remove DCM from the solid-phase synthesizer equipped with 2-Cl-Trt resin;
[0087] 3) Dissolve 0.5 mmol of Fmoc-protected amino acid (Fmoc-Tyr(tbu)-OH) in 10 mL of anhydrous DCM, add 1 mmol of DIEPA, then transfer to the above solid-phase synthesizer, and react at room temperature for 1 h;
[0088] 4) Sealing: remove the reaction solution in the solid-phase synthesizer with ear washing balls, then wash with 10 mL of anhydrous DCM, each for 1 min, for a total of 5 washes, and add the prepared volume ratio of anhydrous DCM: DIEPA: methanol as 17:1:2 solution 20mL, react at room te...
Embodiment 2
[0095] Example 2 Polypeptide indoximod-G D F D F D Synthesis of Y
[0096] It was synthesized according to the solid-phase synthesis method of Fmoc-short peptide in Example 1. Get the polypeptide indoximod-G D F D F D Y. The polypeptide obtained in Example 2 was detected by high-performance liquid chromatography-mass spectrometry, and the results were shown in figure 2 , the structural formula is
[0097]
Embodiment 3
[0098] Example 3 Polypeptide indoximod-G D F D F D Y- D N D Y D S D K D P D T D D D R D Q D Y D H D Synthesis of F
[0099] It was synthesized according to the solid-phase synthesis method of Fmoc-short peptide in Example 1. due to specific binding to the PD-L1 protein on the surface of cancer cells D The PPA-1 sequence is D N D Y D S D K D P D T D D D R D Q D Y D H D F, so the polypeptide of this application is abbreviated as indoximod-G D F D F D Y- D PPA-1. The polypeptide obtained in Example 3 was detected by high-performance liquid chromatography-mass spectrometry, and the results were shown in image 3 , the structural formula of the polypeptide in this example 3 is
[0100]
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Abstract
The invention relates to the technical field of biological medicine. The invention provides an immune polypeptide and application thereof, the immune polypeptide is obtained by connecting an end-capping group and a short peptide, and the short peptide is one or more of GFFY, GDFDFDY and DPPA-1. The immune polypeptide can be self-assembled to form a supramolecular nano-drug. After entering a tumor microenvironment, the supramolecular nano-drug can simultaneously reverse an immunosuppressive effect mediated by accumulation of metabolites such as excessive consumption of tryptophan and kynurenine in an IDO pathway; the nano-drug can be specifically combined with PD-L1 on the surface of cancer cells to block immune escape of tumor cells; meanwhile, the immune response of the organism is activated and enhanced, the three parts play a role in parallel, so that the organism generates strong immune response aiming at tumors, the optimal effect is achieved in cancer immunotherapy, and a new thought is provided for developing multifunctional tumor immunotherapy nano-drugs.
Description
technical field [0001] The invention relates to the technical field of biomedicine, in particular to an immune polypeptide and its application. Background technique [0002] Tumor immunotherapy mainly controls and kills tumor cells by stimulating the body's own immune system, restoring suppressed immune responses, blocking immune escape, or enhancing self-anti-tumor immunity. Among the many immunotherapies, immune checkpoint therapy shines brightly. While immune checkpoint inhibitors targeting PD-1 / PD-L1 have achieved significant efficacy, research on small molecule inhibitors such as short peptide antagonists has also increased. With the deepening of research, more immune checkpoints in the tumor immune microenvironment have been discovered. Studies have shown that indoleamine-2,3-dioxygenase 1 (IDO1) is the key rate-limiting enzyme that catalyzes the metabolism of the essential amino acid tryptophan through the kynurenine pathway, and is also a phenomenon associated with...
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