X-ray diffraction studies using a novel synthetic phospholipid

A novel brominated phospholipid has been designed and synthesised for future use in X-ray diffraction studies. It is an analogue of dipalmitoyl-phosphatidylcholine (DPPC), with the sn-2 chain terminal methyl group exchanged for a bromine atom. This bromine atom "label" has been incorporated into a phospholipid by substitution for a group of similar atomic radius, 1.85 versus 2.00 Å, thus creating a molecule which is sterically similar to its unlabelled analogue. The "bromolipid" has been studied using the swelling series method in conjunction with Patterson mapping in the gel phase at 20°C. It diffracts well to 12 orders in its pure form at 20°C and between 57% and 98% relative humidity. A combination of two phasing methods have allowed the diffraction patterns of bilayers incorporating the bromolipid to be phased unambiguously. We suggest that the bromolipid is excellently suited as a phasing agent for use in future isomorphous replacement and multiple anomalous diffraction (MAD) experiments.