Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Chemical library aids in developing drug system for nerve damage

13.04.2005


A researcher studying drug design for nerve damage therapies has gotten her answer to questions by following some old advice: she used the library.

It’s not the kind of library her mother or teacher suggested, but a combinatorial chemistry library of many different protein sequences that some day might help her and her colleagues develop a successful timed drug delivery system.

Shelly Sakiyama-Elbert, Ph.D., assistant professor of biomedical engineering at Washington University in St. Louis, has screened a large number of molecules to find which ones have varying affinity, or attraction, to a sugar that binds nerve repair drugs called heparin, as well as a nerve repair protein called nerve growth factor.



Sakiyama-Elbert ran a library of viruses called bacteriophage that contained small random portions, or sequences of their surface proteins — which could be used to attract or bind other proteins — through a column with the drug bound to it. She then made the playing field more difficult for the bacteriophage to bind so that eventually she could find bacteriophage peptides that bound to heparin or nerve growth factor. By repeating this process numerous times, she identified peptide sequences that have low, medium or high affinity for the heparin drug.

Looking for good protein sequences

Sakiyama-Elbert and her colleagues are looking for protein sequences that bind to drugs to help a drug delivery vehicle provide timed release of a drug. Such drug delivery systems are called affinity-based, and it is hoped that eventually they will provide the signals necessary to stimulate tissue regeneration for conditions such as nerve damage on an appropriate time scale.

In conjunction with the sequence technique, Sakiyama-Elbert and her group developed a mathematical model that identifies the kind of drug release desired as a basis to narrow down the range of affinities they want to identify from the library. Between the modeling and future experimental studies, they hope to refine their drug delivery design to get the optimal rate of drug release.

"We started with a model I’d previously developed, then added in some features that allow us to model degradation of the delivery system by enzymes," Sakiyama-Elbert said. "Specifically, we added a component where we can model what would happen if there is a cell in part of the delivery system and how that would affect release throughout the delivery system.

"Before you only could address what would happen in a culture dish with no cells around it. We’re really interested in what will happen in cell culture or an animal model where there will be active cell-mediated degradation. We are trying to get closer to the real situation." The results were published in the January 2005 issue of Acta Biomateriali. The work was supported by a grant from the Whitaker Foundation.

Sakiyama-Elbert said lots of researchers are adopting the concept of affinity-based drug delivery systems, and the Washington University library screening technique and mathematical model together provide a good tool to expand the usefulness of these approaches.

"One interesting thing we’ve found in this work is that it appears the activities of the drugs that we’re delivering vary with the affinity of the binding site," she said. "We’re not sure if that’s a function of the affinity controlling the rate of release or if there is actually some separate biological modulator that’s being affected.

"The good thing, though, is that we’ve identified several different affinities of binding sites so we can now test whether it’s the affinity or the rate of release and determine what’s really going on."

This ability is important for researchers to get insight into the biological activity of different drugs and how they might be modulated for drug release.

"We have low, medium and high affinity binding proteins," Sakiyama-Elbert. "We can look at fast and slow release rate for all three of them, so we can control affinity and concentration to our advantage."

Tony Fitzpatrick | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>