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.
Scientists from the UK have been given vital insight into how a large number of drugs are impeded from reaching their targets by the protein Human Serum Albumin (HSA).
They 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.
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. HSA is a particularly difficult protein to crystallise because it is a flexible molecule.
This is the first time that scientists have succeeded in completing a survey of the binding modes of a range of drugs, although HSA's structure has been known for over 10 years.
"This is the first time we have been able to see high resolution images of HSA interacting with different drugs," said Dr Stephen Curry, lead researcher on the study from Imperial's Biophysics Group.
"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 is found at high concentrations in blood plasma and its primary function is to transport molecules of fat around the body.
The protein also binds tightly to a wide range of different drugs, preventing them from travelling to their destination.
"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," Curry added.
"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 results reported in the paper are the result of more than five years' work by a number of University of Imperial students and postdoctoral scientists in Curry's team.
The research is published tomorrow in the Journal of Molecular Biology.