Molecular Imprints Could Change Drugs Science

Thursday, 26 October, 2000

The creation of designer plastic drugs, with the potential for reduced side-effects, is the aim of one team of scientists in the UK.

The precursor to achieving this goal has been the refinement of a technique known as molecular imprinting, where imprints of individual molecules are formed in plastics to create molecularly imprinted polymers (MIPs).

MIPs acting in the role of embryonic plastic drugs, have been shown to reduce and amplify the growth of yeast cells. This potentially opens up a route to a new class of low side-effect, highly specific, plastic drugs.

Although the methodologies behind molecular imprinting are well established, the Cardiff team has taken an important lead in their development and exploitation.

A breakthrough came for the group after it turned the traditional approach to imprinting on its head by looking at apolar, as opposed to polar interactions, to try and maximise the attraction between the molecule of interest and the component parts of the polymers. Previously, apolar interactions had been largely ignored because it is generally believed that, alone, they do not provide sufficient driving force to produce a useful molecular imprint.

The Cardiff team has had some positive results. Polar interactions occur as a result of the presence of charge differences residing in the different functional groups contained in organic molecules. Apolar interactions, as their name implies, result between uncharged species and are generally less strong than polar interactions.

The main advantage of the Cardiff approach is with the type of molecule that can be examined. With the polar variety this is confined to molecules containing functional groups, often acidic or basis in nature, within which the charge resides.

By using apolar interactions the search can be extended to very simple non-functional molecules such as polyaromatic hydrocarbons, which are flat molecules with no functional character.

The team is soon to mount an investigation into the viability of large-scale, selective, environmental clean-up using MIPs, since the exponential growth of international research into molecular imprinting is beginning to move into commercial applications.

The first solid phase extraction, chromatography-type applications are now on the market and several other products are expected.

MIP diagnostic medical sensors are being developed for use in urinary and transcutaneous (the migration of very small amounts of a systemic drug through the skin) monitoring.

The group is also working with molecularly imprinted drug discovery systems where the imprinted polymer is used as a biological receptor mimic. These materials can be used to identify, from a complex mixture or for individual samples, potential drug candidates on the basis of their affinity for the molecularly imprinted receptor mimic.

The scientists are particularly interested in compounds that may be active against certain types of cancers and - through a collaboration with Dr Dan Rathbone at Aston University, English Midlands - the Cardiff team is using imprinted materials to screen libraries of thousands of compounds in search of new drugs for use against tuberculosis.

A similar strategy is being used to identify active compounds of the human immunodeficiency virus (HIV) and a scaled-up version is to be used in their purification.

Other projects have prepared histamine and ephedrine receptor mimics for use in the drug discovery process.

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