Technetium and rhenium coupled tri-and tetrapeptide combinational library, tis active peptide compound and its foundation method

A technology of combinatorial library and peptide compound, applied in technetium, tetrapeptide combinatorial library and its active peptide compound and establishment, rhenium coupling three fields, can solve unreported, unable to use nuclear medicine imaging or treatment, loss of polypeptide activity, etc. problems, to achieve the effect of simple preparation, ideal distribution in vivo, and good physical properties

Inactive Publication Date: 2004-07-28
SHANGHAI CHEST HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It has been reported that labeling known active polypeptides, especially small molecule tripeptides and tetrapeptides, with technetium or rhenium, the activity of the polypeptides will be lost due to changes in molecular structure, so they cannot be used for nuclear medicine imaging or treatment
So far, the related technology of establishing technetium or rhenium-coupled tripeptide and tetrapeptide combinatorial libraries has not been reported domestically or internationally.

Method used

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  • Technetium and rhenium coupled tri-and tetrapeptide combinational library, tis active peptide compound and its foundation method
  • Technetium and rhenium coupled tri-and tetrapeptide combinational library, tis active peptide compound and its foundation method
  • Technetium and rhenium coupled tri-and tetrapeptide combinational library, tis active peptide compound and its foundation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] The exchange method establishes the composition of 19 kinds of L-amino acids 99m Tc-coupled tetrapeptide combinatorial library was screened with human lung adenocarcinoma cell line H1299. Table 1 is predicted to be taken up by human lung adenocarcinoma cell line H1299 99m Tc couples the active amino acids at the four positions of the tetrapeptide compound. Screening found that the closer to the tetrapeptide NH 3 The active amino acid at the terminal concentrates on the cell 99m The more important the Tc-coupled tetrapeptide compound, the lower the cellular uptake closer to the COOH terminus. exist 99m On the position of Tc-coupled tetrapeptide compound, active amino acids M, Q, R, S at position 1 and active amino acids Q and V at position 3 are more effective for cell uptake than active amino acids at other positions 99m Tc-coupled tetrapeptide compounds are more specific. The amino acid at the end of COOH is 99m The in vivo distribution profile of the Tc-coupled...

Embodiment 2

[0074] Construction of Technetium-Coupled Tripeptide and Tetrapeptide Combinatorial Libraries by Exchange Method

[0075] Establish 99m Tc-Coupled Tetrapeptide Combinatorial Library

[0076] Dissolve 50 μg of the tetrapeptide combinatorial library in 0.2 ml of PBS, pH = 7.4, add 3 mg of the weak coupling compound sodium potassium tartrate dropwise, and then add 50 μg of SnCl 2 .2H 2 Add 37MBq (1mCi) immediately after O 99m TCO 4 - For the eluent, seal the vacuum bottle and react in a water bath at 100°C for 10 minutes. Screened by human lung adenocarcinoma cell line H1299 99m Tc-coupled tetrapeptide combinatorial library. The screening results showed that the cells 99m The Tc-coupled tetrapeptide combinatorial library has very significant uptake, confirming that the exchange method can construct a complete 99m Tc-coupled tetrapeptide combinatorial library, formed by 99m Tc-coupled tetrapeptide compounds can be taken up by cells and thus can be screened for activity ...

Embodiment 3

[0086] test 99m Tc coupling tetrapeptide mixture ---- 99m Tc-MX 1 x 2 Y, 99m Tc-QX 1 x 2 Y, 99m Tc-RX 1 x 2 Y, 99m Tc-SX 1 x 2 Y, determine the composition of the active amino acid (M, Q, R, S) at the first position 99m In vivo distribution characteristics of Tc-coupled tetrapeptides, where X 1 is the active amino acid mixture (A, D, E, I, K, N) at the second position, X 2 is the active amino acid mixture (Q, V) at the third position.

[0087] Four nude mice bearing H1299 tumors were subjected to 99m Tc-MX 1 x 2 Y, 99m Tc-QX 1 x 2 Y, 99m Tc-RX 1 x 2 Y, 99m Tc-SX 1 x 2 In vivo imaging study of Y, SPECT image acquisition, the acquisition matrix is ​​256×256, the Zoom is 3.2, and the γ cumulative count is ≥150K.

[0088] The image acquisition methods in the following embodiments are all consistent.

[0089] The imaging results show:

[0090] tumor uptake rate 99m Tc-RX 1 x 2 Y≥ 99m Tc-SX 1 x 2 Y> 99m Tc-MX 1 x 2 Y> 99m Tc-QX 1 x 2 Y;

[00...

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Abstract

The present invention belongs to the field of pharmaceutical chemistry and nuclear medicine, in particular, it relates to technetium or rhenium coupled tripeptide and tetrapeptide combination library, its active peptide compound and its construction method. It includes the following steps: 1. constructing technetium or rhenium coupled tripeptide and tetrapiptide combination library technique; 2. using cell or biological molecule to screen the technetium or rhenium coupled tripeptide and tetrapeptide combination library; 3. screening so as to obtain the active technitium or rhenium coupled tripeptide and tetrapeptide compound. It cna be used for developing technetium or rhenium coupled tripeptide and tetrapeptide compound which can be used for nuclear medicine development and curing radioactive and non-radioactive diseases.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry and nuclear medicine, and specifically relates to a technetium-rhenium coupled tri- and tetra-peptide combination library and its active peptide compound and establishment method. Background technique [0002] Combinatorial peptide library technology originated from the report of Houghten RA and Lam KS in 1991, after which many active peptides were discovered through this technology. It has been reported that labeling known active polypeptides, especially small-molecule tripeptides and tetrapeptides, with technetium or rhenium would result in the loss of activity of the polypeptide due to changes in molecular structure, so it cannot be used for nuclear medicine imaging or treatment. So far, there are no reports on the related technologies of establishing technetium or rhenium-coupled tripeptide and tetrapeptide combinatorial libraries at home and abroad. Contents of the invention [0003] The...

Claims

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Application Information

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IPC IPC(8): C07K5/08C07K5/10
Inventor 曾骏
Owner SHANGHAI CHEST HOSPITAL
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