A method of generating metal chelating affinity ligands

摘要

The present invention relates to a method of generating at least one polydentate metal chelating affinity ligand, which method comprises the steps of:

a) providing at least one scaffold of general formula (I): wherein X1, X2, and X3 irrespective of each other are sp<2> or sp<3> hybridised C atoms or N, S, O or Si, X4 is a nucleophile and m is an integer of 0-2.

b) providing at least one polydentate ligand, optionally in a form wherein the metal chelating functionalities are protected, by derivatisation of the nucleophilic X4 groups of each scaffold, while retaining the cyclic structure of the scaffold;

c) ring-opening at the bond between the carbonyl and the sulfur of the derivatised scaffold by adding a reagent that adds one or more metal chelating affinity ligand arms to the scaffold; and, if required,

d) deprotecting the functionalities of the ligand arm(s) provided in step b). Steps c) and d) may be performed simultaneously. The preferred scaffold (I) is homocysteine thiolactone. The preferred reagent for step b) is bromoacetic acid ethyl ester. Step c) may be effected by treatment with a base such as NaOH. The ligand produced in step d) may be attached to a suitable solid support base matrix. Optionally, the thiol group of the ligand may be attached to such a matrix via reaction with allyl glycidyl ether (AGE).