TECHNOLOGY - Structure Analysis

Structural information facilitates the design of small molecule therapeutics and has been widely used by the industry for soluble protein targets such as kinases and proteases. It has however been difficult to prepare and crystallise sufficient quantities of membrane proteins for structural analysis. The M-FOLD™ platform provides a basis for achieving this, as it is able to deliver membrane proteins in a stable, purified state in multi-milligram amounts.

The Company has programs to elucidate the structures of GPCRs and ion channels using X-ray crystallography and NMR spectroscopy. To date, crystals have been produced for 4 GPCRs and 1 potassium ion channel and preliminary diffraction data has been obtained for a potassium channel.

Crystals of a refolded potassium channel



The Company is also engaged in collaborative studies with ProspectPharma and Stan Opella (UCSD) to explore the use of NMR for structural analysis of GPCRs. Preliminary studies using solid state NMR data for CXCR1 are highly promising and have recently been published.

(A) Solid-state NMR spectrum of CXCR1 in magnetically aligned bicelles. (B) Two-dimensional PISEMA spectrum of a 15N Ile-labeled sample



Reproduced from: J. Am. Chem. Soc. 128:7402 (2006)