| 摘要 |
The disclosure relates to the field of candidate drug testing and drug development. A method is provided for providing a compound composed of at least one molecule attached via at least two linkages to a molecular scaffold, the method comprising providing a scaffold comprising at least a first and a second reactive group; providing at least one molecule capable of reacting with the at least first and second reactive group; contacting the scaffold with at least one molecule to form at least two linkages between the scaffold and the at least one molecule in a coupling reaction, wherein the formation of a linkage accelerates the formation of a consecutive linkage, preferably wherein the coupling reaction is performed in solution, more preferably in an aqueous solution. Furthermore, a method is provided for selecting a candidate drug compound comprising providing a library of compounds hereof and determining the binding of a target molecule to the compounds. |
| 主权项 |
1. A method for preparing a library comprising a plurality of compounds composed of at least one peptide structure attached via at least two thioether linkages to a (hetero)aromatic molecule, the method comprising:
providing at least two compounds, each compound comprising at least one peptide structure attached via at least two thioether linkages to a (hetero)aromatic molecule using a method comprising:
providing a (hetero)aromatic molecule comprising a bis-, tris-, or tetrakis(halomethyl)-substituted (hetero)aromatic ring system;providing at least one peptide comprising at least one amino acid having a side chain comprising an unprotected functional group selected from the group consisting of amine, guanidinium, amido, carboxylic acid, alcohol, phenol, indole, thioether, and imidazole, and at least two SH-functionalities; andcontacting the (hetero)aromatic molecule with the at least one peptide in a buffered aqueous solution comprising at least 50% water to form, in a coupling reaction, at least two thioether linkages between the (hetero)aromatic molecule and the at least one peptide, wherein each of the thioether linkages is formed between one of the halomethyl substituents on the (hetero)aromatic ring system and one of the SH functionalities in the peptide, thus preparing a library comprising a plurality of compounds composed of at least one peptide structure attached via at least two thioether linkages to the (hetero)aromatic molecule. |
