Featured Research

from universities, journals, and other organizations

Nuclear magnetic resonance aids in drug design

Date:
May 20, 2010
Source:
University of Notre Dame
Summary:
A new study is using nuclear magnetic imaging, to move drug design into groundbreaking consideration of the dynamic flexibility of drugs and their targets.

A new study by a team of researchers led by Jeffrey Peng, assistant professor of chemistry and biochemistry at the University of Notre Dame, is using Nuclear Magnetic Resonance (NMR), to move drug design into groundbreaking consideration of the dynamic flexibility of drugs and their targets.

Related Articles


The research, which was published by the Journal of the American Chemical Society, contributes to the growing attention given toward the shape-shifting movement of molecules, a feature that potentially could help drug designers overcome issues of resistance, transportation of drugs to targets and oral bioavailability.

"The new focus is that it's not enough just to look at the protein motion," Peng said. "Of course, we've studied protein motions for some time, as many disease-related proteins are flexible. But we've also realized that in order to impact drug discovery, we also have to look at the candidate drug molecule that is being designed, that is, the 'ligand.' It can move too."

Drug design involves iterative changes of a ligand to optimize its drug-like properties, which include, among other issues, the ability to cross biological membranes and bind specifically to a drug-target, usually a protein. The rules for doing this are well-established for rigid ligands, but much less so for flexible ligands, which turn out to be common starting points for many drug-targets.

"Understanding that lets us predict how flexibility can affect drug-like properties, and how that flexibility should be manipulated in drug design is still elusive," Peng said.

"We need experimental methods that can tell us, systematically, how architectural changes in the candidate drug molecule can change its flexibility relevant for drug-like properties. These methods would benefit not just one particular kind of disease but basically drug design in general," including therapies for cancer, AIDS and MRSA.

"The paper is a beginning of how to systematically understand how we should make ligand molecules, candidate drug molecules, floppy or not floppy, in order to best interfere with the target protein. For example, we can test the idea that some residual 'floppiness' in a drug may help it co-adapt with a protein target site that 'morphs' over time, on account of drug-resistant mutations. We can also study how drug 'floppiness' can affect its ability to cross biological membranes and reach its protein target."

Peng, who worked as a biophysicist at a pharmaceutical company for 10 years before he came to Notre Dame, said the study of flexibility-activity relationships (FARs) adds another dimension to the longstanding structure-activity relationships (SARs) that scientists have studied. Addressing the dynamism of both the target molecule and the drug molecule can provide important resources for drug designers.

"If you could know, atom by atom, which parts have to move and which do not have to move to bind to a target protein, that's information a chemist can use," he says. "They can change the ligand as chemists do, repeat the activity assay, and see if it has improved."

The research was funded by the National Institutes of Health and is part of a collaboration between the Peng laboratory and the laboratory of Felicia Etzkorn at Virginia Tech.


Story Source:

The above story is based on materials provided by University of Notre Dame. Note: Materials may be edited for content and length.


Journal Reference:

  1. Andrew T. Namanja, Xiaodong J. Wang, Bailing Xu, Ana Y. Mercedes-Camacho, Brian D. Wilson, Kimberly A. Wilson, Felicia A. Etzkorn, Jeffrey W. Peng. Toward Flexibility Activity Relationships by NMR Spectroscopy: Dynamics of Pin1 Ligands. Journal of the American Chemical Society, 2010; 132 (16): 5607 DOI: 10.1021/ja9096779

Cite This Page:

University of Notre Dame. "Nuclear magnetic resonance aids in drug design." ScienceDaily. ScienceDaily, 20 May 2010. <www.sciencedaily.com/releases/2010/05/100519163838.htm>.
University of Notre Dame. (2010, May 20). Nuclear magnetic resonance aids in drug design. ScienceDaily. Retrieved December 21, 2014 from www.sciencedaily.com/releases/2010/05/100519163838.htm
University of Notre Dame. "Nuclear magnetic resonance aids in drug design." ScienceDaily. www.sciencedaily.com/releases/2010/05/100519163838.htm (accessed December 21, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, December 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins