A chance discovery by a team of scientists using optical probes means
that changes in cells in the human body could now be seen in a
completely different light.
Prof David Parker from Durham University’s Chemistry Department was
working with experts from Glasgow University, and a team of
international researchers, when they discovered dramatic changes in the
way that light was emitted by optical probes during a series of
Light has energy and carries information and the researchers used
the optical probes to measure the behaviour of light and its
interaction with proteins abundant in human blood. The fortuitous
discovery has led to the creation of a new type of probe for examining
protein interactions that could be used for cellular imaging.
By tracking the way in which proteins bind, the experiments will aid
understanding of the function of the most abundant protein in the body,
serum albumin. In the future the technique could help to understand how
drugs used in medicine interact with the major protein found in blood.
Prof Parker says: "It’s a new step in the development of optical
probes in chemistry and in observing the interaction between medical
drugs and proteins."
The Durham University-led team looked at how light behaved when
serum albumin was added to the probes and found that the emitted
polarised light had interesting characteristics.
Chirality, or handedness, is a key concept in Nature. In molecular
chemistry, it refers to the concept of a molecule having two mirror
images that cannot be superimposed onto each other; these are called
enantiomers and pairs of these can be designated as ‘right-‘ and
Light can be thought of as being made up of two left and right
handed components and this property can be measured. The research team
used optical probes with hi-spatial resolution and precision to track
protein interactions and to see how the light rotates and inverts when
passed through the proteins.
Prof Parker says: "We have found a way to use the inherent chirality
of light to examine the interaction at the molecular level between a
probe (the optical probe, itself of one handedness) and serum albumin
(also of one handedness: hence akin to a hand/glove interaction) – the
most abundant protein in blood."
Based on a chiral lanthanide complex, the probe emits circularly
polarised light that inverts sign on protein binding; monitoring the
emitted light allows researchers to follow the interaction between the
complex and the protein.
Observing this luminescence is a way of studying the chirality of
the system, explains Prof Parker: "The optical signal we observed
carries information in its circular polarisation. It’s a tricky
process. You have to get the light in and out of the cells but
crucially, in terms of biology, it can be done using microscopes in the
laboratory so it’s non-invasive."
The researchers found that only one enantiomer of certain europium
and terbium complexes bound selectively to a drug binding site of the
protein serum albumin, and that the luminescence changed dramatically.
Prof Parker says: "This is the first example of chiral inversion using
an emissive probe in this way."
The researchers have been seeking to develop responsive optical
probes for a while and were delighted when they finally cracked it.
Prof Parker said: "We were genuinely surprised. The binding energy
and kinetics have to be just right – we’ve been lucky. Potentially this
technology could be used to track protein association in living cells
in real time."
Source : Durham University. November 2008.