Scientists at Imperial College London have announced that the research, published in the Journal of Molecular Biology, gives a vital insight into how a large number of drugs are impeded from reaching their targets by the protein Human Serum Albumin (HSA).
Scientists have produced detailed three-dimensional images showing how HSA binds twelve different drugs including ibuprofen, diazepam and warfarin.
This information should help scientists to modify the structures of drugs to improve their effectiveness.
Dr Stephen Curry, lead researcher on the study from Imperial's Biophysics Group, said, “This is the first time we have been able to see high resolution images of HSA interacting with different drugs.”
“Working out which features of HSA are responsible for binding drugs may make it possible to change the design of the drugs so they cannot be bound so easily.”
HSA's ability to bind a variety of drugs often presents a serious problem during the development of new medicines.
If a drug binds too tightly to HSA, it can get trapped in the bloodstream, meaning higher doses are needed to ensure that the drug's benefits are felt.
Ideally, doses should be as low as possible to reduce the risks of toxicity or other side-effects.
Dr Curry adds, “Usually drug companies want to prevent HSA from limiting the concentration of drug being released into the body.”
“Our new information should help them to design features into new drugs to achieve this.”
“However, sometimes the binding properties of HSA can be useful if you want to create a reservoir of drug that can be released slowly and our results should help here too.”
The structures of the HSA-drug complexes were determined using X-ray crystallography, a complex and delicate procedure whereby small protein crystals are grown after adding each drug to a purified preparation of the protein.
Scientists then work out the detailed atomic structure, showing how the drug binds to the protein, by shining x-rays onto the crystal and analysing how these are scattered.