探花直播

Enzymes are biological catalysts 鈥� molecules that speed up chemical reactions within living materials. Many enzymes are already well characterised and their functions fairly well understood. For example, the enzyme known as MMP8 is present in the connective tissue of most mammals, where it breaks the chemical bonds found in collagen.

In pre-clinical research published in the journal Chemistry & Biology, Dr Florian Hollfelder from the Department of Biochemistry at Cambridge and Dr Lutz Jermutus,Senior Director, Research and Development at MedImmune, led a study to map a list of human enzymes (proteases) against potential protein drug targets.

Using automation technology at MedImmune, the team then tested each of the enzymes against each target protein in turn, allowing them to identify a significant number of so-far unknown interactions.

Of particular interest was how MMP8 was able to disable a molecule known as IL-13, which is known to play an important role in several inflammatory diseases such as asthma and dermatitis. 探花直播researchers believe this may be a previously-unknown way in which the body regulates the action of IL-13, preventing these diseases in the majority of individuals. If so, it could provide an interesting target for new drugs against these common diseases.

鈥淢MP8 is well-known to biochemists and we all thought we understood its function, but it鈥檚 clear that this 鈥� and probably many other enzymes 鈥� 鈥榤oonlight鈥� and have several functions within the body,鈥� explains Dr Hollfelder. 鈥淏ecause the enzyme already had a 鈥榥ame鈥� and a function, nobody thought to see if it had a promiscuous side.鈥�

Designing new enzymes has proven an extremely difficult technical challenge, hence the drive to find new uses for previously 鈥榰nderstood鈥� enzymes. By focusing on human proteases, rather than bacterial proteases 鈥� which are actually easier to source 鈥� the researchers are confident that their research will be far more applicable to drug discovery.

鈥淥ur approach is new: we 鈥榬ecycle鈥� known enzymes and ask whether they can do other things than the ones they are known for,鈥� adds Dr Jermutus. 鈥淚n fact, we believe we have found other enzymes that could be similarly deployed against other disease-causing proteins, and this approach, if expanded, could provide further leads for new drugs.鈥�

Commenting on the benefits of the collaboration with industry, Dr Hollfelder adds: 鈥淲ithout MedImmune, our work would have stopped after seeing and characterising the interactions. 探花直播additional extension to cell and mouse models would have been inconceivable in my basic science group.鈥�

Reference
Urbach, C et al. . Chemistry & Biology; 19 Nov 2015