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.