Ligand screening and design by X-ray crystallography
US6297021A · kind A · utility
Assignee
Inventors
Key dates
| Filing date | Mar 5, 1999 |
| Grant date | Oct 2, 2001 |
| Priority date | — |
| Expiry date | Mar 5, 2019 |
Classification
- Technology area (CPC G)Physics
- CPC primaryG01N2500/00
- WIPO fieldMeasurement
- WIPO sectorInstruments
Abstract
X-ray crystallography can be used to screen compounds that are not known ligands of a target biomolecule for their ability to bind the target biomolecule. The method includes obtaining a crystal of a target biomolecule; exposing the target biomolecule crystal to one or more test samples; and obtaining an X-ray crystal diffraction pattern to determine whether a ligand/receptor complex is formed. The target is exposed to the test samples by either co-crystallizing a biomolecule in the presence of one or more test samples or soaking the biomolecule crystal in a solution of one or more test samples. In another embodiment, structural information from ligand/receptor complexes are used to design ligands that bind tighter, that bind more specifically, that have better biological activity or that have better safety profile. A further embodiment of the invention comprises identifying or designing biologically-active moieties by the instant process. In a further embodiment, a biomolecule crystal having an easily accessible active site is formed by co-crystallizing the biomolecule with a degradable ligand and degrading the ligand.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.