Making drugs on proteins: site-directed ligand discovery for fragment-based lead assembly |
| |
Authors: | Erlanson Daniel A Hansen Stig K |
| |
Institution: | Sunesis Pharmaceuticals, Inc., 341 Oyster Point Boulevard, South San Francisco, California 94080, USA. erlanson@sunesis.com |
| |
Abstract: | Rapid progress in genomics and proteomics has provided a wealth of new targets for the pharmaceutical industry, even as many older targets still remain challenging for small-molecule drug discovery. Fragment-based lead discovery, in which leads are built progressively by expanding or combining small fragments, is a rapidly growing field that offers potential advantages over traditional lead-discovery processes. However, identifying and assembling the fragments themselves can be challenging. Here, we review the concept of site-directed ligand discovery, in which a covalent bond is used to stabilize the interaction between a low-affinity fragment and a target protein. We also describe how this technique can facilitate fragment-based lead discovery and help overcome some of the limitations of traditional screening methods. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|