ENGINEERS have devised a way to make drug testing more efficient and affordable. The new drug discovery method could be used to combat antibiotic resistance.
The testing that is currently done for discovering new medication involves a process where thousands of drug candidates are tested in rapid succession to see how they interact with a sample of a target disease. The next stage involves more time consuming and expensive tests to follow up on any promising candidates identified during the first stage.
During the first stage, it is possible for drug candidates to stick together to form an aggregate that physically, rather than chemically, inhibits the activity of the sample. These are known as “promiscuous inhibitors” and can generate false positives which are only identified during the slower second stage.
Predicting which drugs are likely to aggregate and form promiscuous inhibitors is extremely difficult, and current computational models are unable to identify which drugs will form aggregates based solely on their physical properties. Differentiating between promiscuous inhibitors, and “true inhibitors” – those that chemically interact with the sample and are genuine candidates for new drugs – is vital for making drug testing more efficient.
Engineers at McMaster University, Canada, have developed a hydrogel that can be printed in thin layers to form a “cage” around the sample molecules. The size of the pores in the cage can be varied so that it can be tailored to block promiscuous inhibitors from coming into contact with the molecule while allowing the true inhibitors through the cage. The printed hydrogel is inexpensive and also allows for a smaller sample size to be used, further reducing costs.
This new method will speed up the discovery of new drugs, particularly those that might address the increasing problem of antibiotic resistance. b-lactam antibiotics are a class of broad-spectrum antibiotics, such as penicillin, which include a b-lactam ring in their molecular structure. Some bacteria produce an enzyme known as b-lactamase that can attack the b-lactam ring and render the antibiotic ineffective. As the hydrogel technique can tell the difference between real and promiscuous inhibitors of b-lactamase, it might be possible to “reclaim” antibiotics that had been rendered ineffective.
"As the next step, we are looking for industry partners to prove the effectiveness of our technology on a full-scale screen of thousands of molecules that can help to extend the lifetime of our current antibiotics," said Todd Hoare from McMaster University. "We are optimistic this approach can help to bring new effective drugs to patients faster than is currently possible".
Nature Communications http://doi.org/ckh9
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