Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Biochips in Drug Development

26.06.2003


Figure 1: Ligand fishing (BIA-MS coupling)


Figure 2: ADME assays of small compounds binding to HSA


Biomolecular interaction analysis (BIA) using SPR (surface plasmon resonance) biosensors is now utilised increasingly in nearly all phases of drug development. The BIA system consists out of a light source emitting near infrared light, a sensor microchip, an automated liquid handling system with constant flow and a diode array position-sensitive detector. One of the two interacting partners (referred to as the ligand) is immobilized on the sensor surface. The other binding partner, called the analyte, is directed over the surface in a constant flow system allowing to monitor the interaction of the binding partners in “real time”.

BIA covers a broad range of applications in target identification and validation, secondary screens and lead optimisation, early ADME assays as well as testing immunoreactivity.

Assay development and functional assays of proteins are the most commonly used areas of applications of BIA in drug development.



Advantages of SPR-based measurements are the possibility to measure in real time without the need of labelling yielding highly reproducible kinetic data with low sample consumption.

Ligand fishing

BIA-technology is ideally suited as a micro-affinity purification platform allowing on-line detection of binding events and the direct quantification of bound material on biological surfaces of interest.

Kinetic parameters may be obtained as additional information. Provided that a binding partner has been captured on the sensor chip it can be recovered by a gentle elution for further downstream analyses like mass spectrometry or western blot analysis (see figure 1).

In comparison to classical chromatographic methods biosensor systems show reduced unspecific binding, are compatible with small volume recovery and are readily automated.

The identification of unknown ligands is of particular interest for revealing function of orphan receptors, for the detection of cellular interaction networks and for testing the biocompatibility of novel surface coatings.

Target validation

Genomics and proteomics based techniques have provided a lot of new potential targets which has to be validated to prove that a DNA, RNA or protein molecule is directly involved in a disease process and is therefore a suitable target for the development of new therapeutic compounds.

The assessment of biological function, involvement in biological pathways and role in pathogenesis of potential targets can be achieved by mapping and validation of protein interaction networks in vivo and in vitro.

Yeast two hybrid and phage display are classical approaches for systematic protein interaction screening capable to probe millions of interactions. Positives obtained from these screening technologies can be validated using BIA technology.

Furthermore, additional parameters relevant for the interaction of interest can be investigated. This could be interactions with multiple components, effects of cofactors, pH-changes or the role of posttranslational modifications.

Lead optimisation

Hit validation is needed to determine whether a molecule identified in a screen or assay will eventually lead to a drug.

Therefore secondary assays generating data about potency, selectivity and functional biochemical activity have to be performed.

BIA technology has an enormous capability for the rapid confirmation of hits from high throughput screens by a comprehensive kinetic characterisation of potential lead compounds.

Information about affinities, rates of association and dissociation in complex formation and binding stoichiometries is very valuable for a ranking and optimisation of lead compounds. Even compounds binding with low affinity or transient kinetics, often found in early phases of drug development, can accurately be identified.

The kinetic information obtained by functional assays together with the knowledge about structural properties of biomolecules allows predictions on structure activity relationships.

Lead optimisation is an iterative process involving computer-assisted molecular modelling, chemical synthesis of new compounds and functional assays.

BIA technology is used in lead optimisation by linking compound structural information with a comprehensive kinetic characterisation of ligand binding.

ADME

ADME assays (adsorption, distribution, metabolism, elimination) become more and more important even in the earlier phases of the drug development process.

BIA assays provide very valuable information for a cost-effective in vitro characterisation of potential drug candidates in early ADME studies, although there are no methods available for accurately predicting what will happen to a drug in vivo.

SPR biosensor technology has already been applied for the binding of potential drug candidates to serum proteins, for analysing the adsorption of small molecules to artificial membranes immobilised on sensor chips and for measuring the influence of compounds on metabolic pathways.

The pharmacokinetic properties of small molecule drugs are a function of the reversible binding to serum proteins such as serum albumin, alpha 1-acid glycoprotein or gamma globulins, reducing the bioavailibility of the drug (see figure 2).

Biaffin offers a BIA assay for analysing the binding of small molecule compounds to high density serum protein surfaces yielding valuable information about affinitiy, solubility and binding stoichiometry of potential drug candidates.

Immune response

Newly designed pharmaceuticals can cause an unwanted immune response. In preclinical studies such potentials can be recognised in animal studies.

BIA technology can detect antibodies against new drugs in animal serum samples. With appropriate control experiments positive binding signals of low antibody levels can clearly be identified as a specific signal despite of the complexity of the protein mixture in serum samples.

Dr. Stephan Drewianka | Biaffin GmbH & Co KG
Further information:
http://www.biaffin.com/drug_development.htm
http://www.innovations-report.de/html/profile/profil-1117.html

More articles from Health and Medicine:

nachricht Custom-tailored strategy against glioblastomas
26.09.2016 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New leukemia treatment offers hope
23.09.2016 | King Abdullah University of Science and Technology

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: First-Ever 3D Printed Excavator Project Advances Large-Scale Additive Manufacturing R&D

Heavy construction machinery is the focus of Oak Ridge National Laboratory’s latest advance in additive manufacturing research. With industry partners and university students, ORNL researchers are designing and producing the world’s first 3D printed excavator, a prototype that will leverage large-scale AM technologies and explore the feasibility of printing with metal alloys.

Increasing the size and speed of metal-based 3D printing techniques, using low-cost alloys like steel and aluminum, could create new industrial applications...

Im Focus: New welding process joins dissimilar sheets better

Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of light metals.
Scientists at the University of Stuttgart have now developed two new process variants that will considerably expand the areas of application for friction stir welding.
Technologie-Lizenz-Büro (TLB) GmbH supports the University of Stuttgart in patenting and marketing its innovations.

Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of...

Im Focus: First quantum photonic circuit with electrically driven light source

Optical quantum computers can revolutionize computer technology. A team of researchers led by scientists from Münster University and KIT now succeeded in putting a quantum optical experimental set-up onto a chip. In doing so, they have met one of the requirements for making it possible to use photonic circuits for optical quantum computers.

Optical quantum computers are what people are pinning their hopes on for tomorrow’s computer technology – whether for tap-proof data encryption, ultrafast...

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Paper – Panacea Green Infrastructure?

30.09.2016 | Event News

HLF: From an experiment to an establishment

29.09.2016 | Event News

European Health Forum Gastein 2016 kicks off today

28.09.2016 | Event News

 
Latest News

First-Ever 3D Printed Excavator Project Advances Large-Scale Additive Manufacturing R&D

30.09.2016 | Materials Sciences

New Technique for Finding Weakness in Earth’s Crust

30.09.2016 | Earth Sciences

Cells migrate collectively by intermittent bursts of activity

30.09.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>