Building in molecular diversity for targeted libraries.
The use of gene-focussed libraries for screening against protein targets can improve timelines for drug discovery projects. This is especially true when the library is based on a novel core scaffold, avoiding the potential need to scaffold hop from early hits. Identification of an appropriate novel scaffold is therefore integral to the success of such a library. In this article we outline a new method to aid scaffold design that combines structure- based virtual screening (VS) with a second phase in which fragmentation of the output is made before the final scaffold design step. Through consideration of a refined set of bound fragments, in the context of the compounds from which they originated, appropriate vectors for appended R-groups can be assigned before validation of the final library.
David W
DW
Sheppard
Jacqueline A
JA
MacRitchie
D015195:Drug Design; D004364:Pharmaceutical Preparations / Q000378:metabolism; D011485:Protein Binding; D054852:Small Molecule Libraries
D004364:Pharmaceutical Preparations; D054852:Small Molecule Libraries