| 摘要 |
A method for synthesizing and screening a lead compound, comprising the following steps: (1) retrieving raw materials: retrieving an i-number of synthetic blocks and an (i+2)-number of single-stranded DNA fragments; (2) synthesizing a compound by using a combinatorial chemistry method, acquiring a library of a single-stranded DNA-marked compound; (3) screening: screening the library of the DNA-marked compound; and, (4) sequencing: retrieving the DNA-marked compound screened in step (3), and sequencing the DNA on the DNA-marked compound, where the synthesis blocks and reaction mechanism of the compound can be determined on the basis of the DNA sequencing. Also disclosed are a synthesis and screening reagent testing kit for the lead compound and a combinatorial chemistry library. |
| 主权项 |
1. A method for synthesizing and screening lead compounds, comprising the following steps of:
(1) Preparing raw materials, i.e., i synthetic building blocks and (i+2) single-stranded DNA fragments, where the (i+2) single-stranded DNA fragments comprise i tag sequences, a start sequence and a terminal sequence, and the i tag sequences specifically tag the i synthetic building blocks, respectively, where i−1, 2, 3 . . . n; (2) Synthesizing a compound library by combinatorial chemistry method: a, preparing initial synthetic building blocks: selecting 1 to i synthetic building blocks, linking one end of the start sequence to a synthetic building block and the other end of the start sequence in series to a specific tag sequence of the synthetic building block, to obtain 1 to i initial synthetic building blocks tagged with single-stranded DNA with a free end; b, synthesizing compounds by reacting the initial synthetic building blocks obtained in step a and the 1 to i synthetic building blocks in a manner of linear combination, wherein, during synthesis, once a new synthetic building block is added, a specific tag sequence of this new synthetic building block is linked in series to the free end of the single-stranded DNA linked to the initial synthetic building blocks such that the single-stranded DNA is gradually lengthened; at the end of synthesis, the terminal sequence is linked in series to the free end of the single-stranded DNA to obtain a single-stranded DNA-encoded compound library; (3) Screening: screening the DNA-encoded compound library to select target compounds; and (4) Sequencing: sequencing the DNA of the target compounds screened in step (3), and determining synthetic building blocks and reaction mechanisms for the target compounds. |
