Membrane receptors, such as the
receptors, and other
membrane components, are the
subject of intense cell biology and drug discovery research.
This is because 60% of all drugs work by interacting with GPCR receptors.
Membrane receptor microarrays would be the ideal tool for drug discovery, as
microarrays enable entire membrane receptor families to be analyzed in a
single experiment. However because previous microarrays were
unable to realistically deal with cell membrane receptors, researchers are
presently forced to use expensive and slow microwell methods.
Microwell methods require large amounts of sample, and
each microwell requires one or more individual operations. As a result,
at present, membrane receptor work is expensive, slow, and laborious.
Molecular Pathways has devised a novel membrane receptor microarray
technology (patent 6,790,632) (text)
overcomes most of the problems associated with earlier membrane microarrays. This
new technology will enable the creation of advanced tools, such as comprehensive GPCR
receptor family microarrays, that will bring new insights to many areas of
modern pharmacology, biology, and medicine.
A CIP of this patent
recently issued that
extends the use of this technology into drug manufacturing process and
analytical technology (PAT) applications.
1000 – 2000 nm diameter liposomes, containing
fluorescent labeled membrane receptors, are bound to a
transparent microarray support surface by anchor groups (not shown). The
support surface is illuminated from below with fluorescent excitation light
(green arrows) aimed at the correct angle to create an evanescent light wave
that penetrates several hundred nanometers into the surrounding medium. The
support surface also contains bound ligands (blue), which bind to the
membrane receptors. In the absence of competing test ligands (left), the
membrane receptors cluster close to the surface, where they receive intense
evanescent excitation energy, and emit an intense fluorescent signal (red
arrows). In the presence of competing test ligands (right), the membrane
receptors release from the surface bound ligands, and diffuse freely over
the surface of the liposome, away from the surface. The evanescent light
decays rapidly with distance. These membrane receptors receive less energy,
and emit a smaller signal.
The microarray is reusable, and multiple types of membrane receptors may be
spotted onto different locations on a single microarray.
A speculative talk, discussing the potential use of this technology for
drug discovery engines, is available here.