Sticky triangles: New tools for experimental phasing of biological macromolecules

X-ray crystallography is the prime method for the elucidation of three-dimensional molecular structures. The determination of novel structures is hampered by the crystallographic phase problem. For biological macromolecules experimental phasing is one technique to solve this phase problem; it usually requires the incorporation of heavy atoms in the protein crystal. In this thesis a new class of compounds was developed that combines heavy atoms for experimental phasing with functional groups for interaction with biological macromolecules. Three functional groups interact with protein residues and make the compounds sticky. Three halogen atoms provide a strong anomalous signal and may be used for experimental phasing. The halogen atoms form an equilateral triangle, which is easily recognised in the heavy-atom substructure. So far several novel protein structures have been solved with the iodine triangle compound. The sticky compounds of the current work are readily available and easy to use.