About Careers MedBlog Contact us
Medindia LOGIN REGISTER
Advertisement

How Drugs can Provide Best Treatment With Fewer Side-Effects

by Bidita Debnath on October 9, 2017 at 11:33 PM
Font : A-A+

How Drugs can Provide Best Treatment With Fewer Side-Effects

Producing a new drug is an expensive and time-consuming process that is subject to extensive regulation. A powerful new way of analysing how drugs interact with molecules in the body could aid the design of better treatments with fewer side-effects.

Most pharmaceuticals work by binding to a small site on the large proteins they target, causing the protein to change shape and so also its activity.

Advertisement


To find drugs that act specifically against a protein without also binding to others that are similar - and so causing side effects - it is important to understand this binding site in detail. Many current techniques can only provide partial information, giving details about which parts of the drug itself are important and, in some cases, the overall structure of the protein.

Researchers at the University of East Anglia have now developed a new approach that can reveal the other side of the jigsaw puzzle - which parts of the protein interact with the drug. It adapts a technique known as ligand-based Nuclear Magnetic Resonance (NMR) spectroscopy to reveal which amino acids in the protein are involved in binding to the drug.
Advertisement

They were able to do this by examining the drug and without having to label the protein, as is required in some other methods.

"Designing novel drugs is a bit like finding the proper piece that fits into a jigsaw puzzle," said Dr Jesus Angulo, a senior lecturer at the University of East Anglia's school of pharmacy who led the research. "It is not just the shape but also graphical content on the piece that must match the surrounding picture.

"Our novel approach allows us to now find the exact piece that matches the complementary shape and graphical content in a protein binding site."

The new NMR technique, which is called DEEP-STD NMR, is described in the journal Angewandte Chemie.

It is based on an existing NMR technique used to study drug-protein interactions called STD-NMR. This works by exciting all of the amino acids in a protein by irradiating them.

It is then possible to look for where this excited state is transferred to chemical sites on the drug when it binds to it. This approach is similar to covering the protein with paint and then pressing the drug against it to see which parts get stained.

But Dr Angulo and his colleagues, whose work was funded by the BBSRC, found it is possible to irradiate the protein with different frequencies to excite different types of amino acid.

This allowed them to unpick which amino acids in the protein's binding site are directly in contact with the drug from the "paint marks" they leave behind.

This means they only have to look at the drug to work out the important parts of the protein that are being targetted. They were able to get further information about the amino acids involved by using a combination of deuterium oxide, or heavy water, and normal water as a solvent.

The team, which included researchers at the Quadram Institute in Norwich, demonstrated their method on two well-studied proteins - an enzyme called intramolecular trans-sialidase, which is produced by a bacterium found in the human gut, and a subunit of the Cholera Toxin.

Dr Angulo said: "Our new method gives researchers a powerful tool to indirectly understand the architecture of the protein binding pocket.

"This will allow them to determine what are the best chemical requirements for a drug to interact specifically with a given protein receptor. This could to lead to stronger and more selective drug candidates, while lower amounts would be needed to trigger the desired effect."

Source: Eurekalert
Advertisement

Advertisement
Advertisement

Recommended Reading

Latest Drug News

 Parkinson's Unmet Needs Creates Path for New Entrants into the Market
Addressing the unmet needs of Parkinson's Disease by providing disease-modifying therapies could bring about a major shift in the way that patients are treated.
How Microrobots Could Help Treat Bladder Diseases?
Microrobots could swirl through a person's blood stream, search for targeted areas to treat for various ailments.
How Can Multivitamin Supplements Slow Cognitive Aging?
Supplementation with multivitamins is an inexpensive way for older adults to slow down memory loss.
 Ivosidenib Approved for Acute Myeloid Leukemia & Advanced Cholangiocarcinoma
Some people with an aggressive blood cancer called acute myeloid leukemia (AML) may soon have a new drug option called Ivosidenib that blocks the activity of IDH1 gene.
Sacubitril/valsartan Unleashes Hope for Heart Failure Patients
In case of cardiac failure where the ejection fraction is greater than 40%, sacubitril/valsartan can prove to be quite beneficial
View All
This site uses cookies to deliver our services.By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use  Ok, Got it. Close
×

How Drugs can Provide Best Treatment With Fewer Side-Effects Personalised Printable Document (PDF)

Please complete this form and we'll send you a personalised information that is requested

You may use this for your own reference or forward it to your friends.

Please use the information prudently. If you are not a medical doctor please remember to consult your healthcare provider as this information is not a substitute for professional advice.

Name *

Email Address *

Country *

Areas of Interests