GENERATION AND SCREENING OF A DYNAMIC COMBINATORIAL LIBRARY

摘要

The present invention concerns a method for selectively establishing a dynamic combinatorial library of ligands for a target which binds at least two functionalities, which method comprises the following steps: selecting a plurality of functionalities which upon combination with each other are capable of forming an entity which may bind to the at least two functionalities in the target; selecting at least one spacer group to be located between the at least two functionalities, which spacer group is of an appropriate size and/or flexibility to allow the functionalities to fit into the binding sites on the target and allowing a reversible bond formation and cleavage; creating discrete ligands by linking at least two identical or different functionalities by at least one spacer group or; linking the functionalities to fragments of the spacer group which contain functions allowing the said reversible bond formation under formation of the spacer group and cleavage of it; mixing together a plurality of different discrete ligands and/or different functionalities; subjecting the mixture to conditions allowing a reversible bond formation and cleavage; adding the target to the mixture; identifying the functionality combinations which are most appropriate for the formation of a complex between the target and the active molecule. In a further embodiment of the invention, the target is added when the discrete ligands are mixed together, in order to be present when the scrambling takes place.