Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Nuclear magnetic resonance aids in drug design

20.05.2010
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.

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.

Contact: Jeffrey Peng, associate professor of chemistry and biochemistry, 574-631-2983, jpeng@nd.edu News

Jeffrey Peng | EurekAlert!
Further information:
http://www.nd.edu

Further reports about: NOTRE Nuclear biological membrane drug molecule

More articles from Studies and Analyses:

nachricht Study relating to materials testing Detecting damages in non-magnetic steel through magnetism
23.07.2018 | Technische Universität Kaiserslautern

nachricht Innovative genetic tests for children with developmental disorders and epilepsy
11.07.2018 | Christian-Albrechts-Universität zu Kiel

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Smallest transistor worldwide switches current with a single atom in solid electrolyte

17.08.2018 | Physics and Astronomy

Robots as Tools and Partners in Rehabilitation

17.08.2018 | Information Technology

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>