The first mechanism disrupts the arrangement of amino acids required for the cohesion of the protease subunits. As a result the protease breaks into two parts. The second acts directly on the core of the active center. It converts the amino acid that does the actual splitting into another kind of amino acid the "scissors" lose their edge and the protein is rendered inoperable. Both approaches inhibit the protease in completely novel ways and are thus very promising for the development of new forms of medication.
The scientists also found a whole series of inhibitors that initiate the two mechanisms. "Knowing the ways in which substances deactivate the proteases is a huge advance," says Gersch. "We can now optimize the substances and possibly also apply the principle to other proteases."
In further research, Gersch and Sieber plan to test their substances on living bacterial strains to determine if these are truly inhibited in growth and pathogenic effect. "Although the bacteria are not completely disarmed, they produce significantly fewer toxins that are conducive to inflammation," says Gersch. "The basic idea is that we give the immune system more time to handle the pathogens on its own while the formation of new resistances is suppressed."
|Contact: Dr. Andreas Battenberg|
Technische Universitaet Muenchen