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Glycosylated somatostatin analogue 123/131I-Gluc-KE108 and preparation method thereof

A 131i-gluc-ke108, gluc-ke108 technology, applied in the preparation methods of peptides, chemical instruments and methods, organic chemistry and other directions, can solve problems such as non-targeting and false negatives

Active Publication Date: 2018-05-11
HTA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the commonly used NETs molecular probes have certain limitations. For example, they are not targeted to NETs without SSTR2 and SSTR5 expression, such as prostate cancer, sarcoma, and inactive pituitary tumors. They are also useful in the diagnosis of some gastroenteropancreatic neuroendocrine tumors. high false negative

Method used

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  • Glycosylated somatostatin analogue 123/131I-Gluc-KE108 and preparation method thereof
  • Glycosylated somatostatin analogue 123/131I-Gluc-KE108 and preparation method thereof
  • Glycosylated somatostatin analogue 123/131I-Gluc-KE108 and preparation method thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Synthesis of Gluc-KE108

[0042] The specific synthetic route of Gluc-KE108 is attached figure 1 As shown, the specific steps are as follows:

[0043] (S1-1) Condensation of amino acids

[0044] Weigh 0.71 g (0.3 mmol) of Fmoc-Phe-CTC Resin, add it to the polypeptide reactor, swell with DMF for 1 h, then add 20% piperidine and react at room temperature for 30 min to remove Fmoc, wash the resin 3 times with DMF, and then add 358mgFmoc-Thr(tBu)-OH, 324mg HBTU, 200μL NMM, after reacting for 50 minutes, it was detected that ninhydrin was negative, filtered and washed to obtain Fmoc-Thr(tBu)-Phe-CTC Resin, repeat the above operation and add the corresponding amino acids in turn: Fmoc- Lys(Boc)-OH(422mg), Fmoc-D-Trp(Boc)-OH(474mg), Fmoc-Phe-OH(349mg), Fmoc-Phe-OH(349mg), Fmoc-Arg(Pbf)-OH (584mg), Fmoc-D-Dab(Dde0-OH (0.454mg), Boc-Tyr(tBu)-OH (304mg), made Boc-Tyr(tBu)-DDab(Dde)-Arg(Pbf)-Phe -Phe-DTrp(Boc)-Lys(Boc)-Thr(tBu)-Phe-CTCResin.

[0045] (S1-2) De-Dde of polypept...

Embodiment 2

[0057] Gluc-KE108 was tested by Iodogen method 123 / 131 I mark:

[0058] The marked tube was pre-coated with 50 μg lodogen, and sequentially added 50 μL of 1 mg / mL Gluc-KE108 in dimethyl sulfoxide solution, 10 μL of 18.5-37 MBq Na 123 / 131 I, shaking reaction for 10 minutes, dissolved with physiological saline. Then use HPLC method or thin-layer chromatography to analyze its labeling rate, and after the product is separated and purified, use HPLC to analyze its radiochemical purity.

Embodiment 3

[0060] Using chloramine-T method (CH-T method) to Gluc-KE108 123 / 131 I mark:

[0061] Dissolve 50 μg Gluc-KE108 in 80 μL 0.5mol / L pH 7.4 phosphate buffer, then add 10 μL 18.5-37MBq Na 123 / 131 I, finally add 10 μL of 10 mg / mL chloramine-T solution. Gently shake the mixture at 20°C for 1-2min, then add 50μL pH7.4 4.0mg / mL sodium metabisulfite solution to stop the reaction. Then use HPLC method or thin layer chromatography to analyze its labeling rate, and after the product is purified, use HPLC to analyze its radiochemical purity.

[0062] In summary, 16.3 mg of Gluc-KE108, i.e. Gluc-Tyr-Cyclo (DDab-Arg-Phe-Phe-DTrp-Lys-Thr-Phe), was synthesized by Fmoc solid-phase synthesis, and the purity was 95.2 mg by HPLC analysis. %, through mass spectrometry, it can be known that m / z is 720.1 ((M+2H) / 2) and 1438.5 (M), consistent with the calculated value (M 计算值 =1438.6), as attached figure 2 And attached image 3 shown.

[0063] Prepared using the Iodogen method 123 / 131 The labe...

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Abstract

The invention belongs to the field of medicines, and concretely relates to a 123 / 131I-labeled novel glycosylated somatostatin analogue 123 / 131I-Gluc-KE108 and a preparation method thereof. The preparation method of the 123 / 131I-labeled novel glycosylated somatostatin analogue 123 / 131I-Gluc-KE108 comprises the following steps: (S1) synthesizing a novel glycosylated somatostatin analogue Gluc-KE108;and (S2) labeling the Gluc-KE108 with 123 / 131I, wherein step (S1) comprises (S1-1) amino acid condensation, (S1-2) removal of Dde from a polypeptide, (S1-3) resection of the polypeptide from resin, (S1-4) cyclisation of the polypeptide, (S1-5) acidolysis of the polypeptide and purification of an intermediate, and (S1-6) glycosylation and purification of the polypeptide; and in step (S2), the Gluc-KE108 is labeled with the 123 / 131I through adopting an Iodogen technology or a chloramine-T technology.

Description

technical field [0001] The invention belongs to the field of medicine, in particular to a 123 / 131 I-labeled novel glycosylated somatostatin analogs 123 / 131 I-Gluc-KE108 and its preparation method. Background technique [0002] Neuroendocrine tumors (Neuroendocrine Tumors, NETs) are a heterogeneous group of tumors originating from different neuroendocrine organs, including a broad lineage from classical carcinoids with good prognosis to highly malignant undifferentiated neuroendocrine carcinomas, 85% of which are derived from In the digestive tract, 10% originate from the lungs, and can still be found in the larynx, thymus, adrenal gland, ovary, skin, prostate and other parts. In recent years, the incidence of NETs has been increasing. Early diagnosis and early treatment are the key to cure this disease. Studies have shown that up to 94% of NETs cells have high expression of somatostatin receptor (SSTR), and even some poorly differentiated tumor cells also have SSTR expres...

Claims

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Application Information

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IPC IPC(8): C07K9/00C07K1/13C07K1/107C07K1/06C07K1/04
CPCC07K9/006
Inventor 郭飞虎李明光李光成伟华李艳涛王成龙冯婷婷樊红强
Owner HTA CO LTD
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