Hitching a ride: misfiring drugs hit the wrong targets
It probably isn't surprising to read that pharmaceutical drugs don't always do what they're supposed to. Adverse side effects are a well-known phenomenon and something many of us will have experienced when taking medicines.
frolicsomepl; pixabay.com; CC0
Sometimes, these side effects can be caused when a drug hits the wrong target, binding to the wrong protein. However, the difficulty of tracking this process means that little research has been carried out.
Now, a new study led by scientists at the University of Oxford and published in Nature Chemistry has shown how a series of anti-HIV protein inhibitor drugs can interfere with the processing of a protein known as prelamin A, essential for maintaining the shape of human cells and directly related to ageing.
The researchers used mass spectrometry – a long-established way of identifying molecules by measuring their mass – to observe directly the drugs' 'hitchhiking' on the wrong protein.
Professor Dame Carol Robinson of Oxford's Department of Chemistry , corresponding author on the paper, said: 'The "hitchhiking" of drugs on incorrect targets is a common problem but isn't much studied, as it can be difficult to observe directly. You have to know which proteins to look for, and only then can you target these proteins for further research.
'The results of this study surprised us, as the drugs target HIV proteases and were not thought to bind the human metalloprotease that is involved in processing prelamin A.'
The researchers found that the anti-HIV drugs lopinavir, ritonavir and amprenavir each blocked the processing of prelamin A.
Professor Robinson added: 'The association between some anti-HIV drugs and premature ageing has been suspected for some time through observation of patients undergoing treatment, but it hasn't been proved at the molecular level. There have also been other highly publicised drugs with off-target protein side effects, including an anti-diabetes drug that caused heart attacks in some patients.
'Now that we have developed this mass spectrometry-based approach, we anticipate that it will have widespread application, since it is likely that many drugs that are designed with a specific target in mind end up hitchhiking on other protein targets. It could even be used during the drug development process to determine if drugs are binding to the wrong targets at the molecular level.'
Original publication
Other news from the department science
Get the analytics and lab tech industry in your inbox
From now on, don't miss a thing: Our newsletter for analytics and lab technology brings you up to date every Tuesday. The latest industry news, product highlights and innovations - compact and easy to understand in your inbox. Researched by us so you don't have to.
Most read news
More news from our other portals
See the theme worlds for related content
Topic World Mass Spectrometry
Mass spectrometry enables us to detect and identify molecules and reveal their structure. Whether in chemistry, biochemistry or forensics - mass spectrometry opens up unexpected insights into the composition of our world. Immerse yourself in the fascinating world of mass spectrometry!
Topic World Mass Spectrometry
Mass spectrometry enables us to detect and identify molecules and reveal their structure. Whether in chemistry, biochemistry or forensics - mass spectrometry opens up unexpected insights into the composition of our world. Immerse yourself in the fascinating world of mass spectrometry!
