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Biologists at the Technical University of Darmstadt have discovered means for speeding the transport of the active ingredients of drugs into live cells that might allow drastically reducing drug dosages in the future.

Drugs do not exhibit their effects until they have been taken up by the associated cells of the organ involved and become available for metabolism there. Although there are numerous, widely differing types of cells, every cell, regardless of its type, is enclosed by a membrane that is permeable by particular substances or particulates only. Biomedical researchers have thus been urgently seeking new means for selectively introducing drugs into cells. Prof. Cristina Cardoso and Dr. Henry D. Hercé, of the Technical University of Darmstadt's biology Dept. have recently made significant progress in that direction in that they have found means for substantially accelerating the transport of substances, particularly water-soluble substances, through cell membranes.

The Darmstadt biologists have been working with short protein chains that drill their way through cell membranes for that past several years. Such miniscule proteins, termed "cell penetrating peptides" (CPPs), may serve as a sort of vehicle for active ingredients of drugs that simply attach themselves to CPPs and are dragged along with the latter into cells.

Cyclic proteins transport drugs faster

In an article that has just appeared in the American journal nature communications (10.1038/ncomms1459), the Darmstadt biologists have shown that cyclic proteins represent particularly good vehicles, since both their transport rates and transport speeds are much greater than those of linear-chain CPPs. In practice, what that means is that, in the future, both drug dosages and the lags until time begin effects might be drugs to exhibit their drastically reduced.

For example, the tiny protein TAT is a flexible, linear chain, whose "backbone" has various, lateral branches appended to it its backbone has a rather large number of degrees of freedom, i.e., is highly flexible, as are its lateral branches. Investigations conducted by the Darmstadt group have shown that transport of entitled through cell membranes is greatly enhanced by a less-flexible, cyclic structure of the transporting vehicle, since the critical factor appears to be that the guanidinium groups in its lateral branches should be spaced at the greatest possible intervals, which is more likely to occur in the case of a cyclic structure, where the vehicle's backbone forms a closed loop and the guanidinium groups thus extend radially outward from the loop. For example, cyclic TAT penetrated cell membranes fifteen minutes sooner than the usual, linear-chain TAT, where closure of the chain improved transport efficiency in the case of both TAT and other arginine-rich CPPs.

In the future, the biologists at the TU Darmstadt plan to study the transport of particular, water-soluble, active ingredients. Remaining to be clarified are how cells deal with cyclic, nano-scale transporter, namely, whether the latter are ejected by cells, decomposed by them, or simply retained by them unchanged, and, finally, whether their studies, which were conducted on cells conditions, will kept under artificial be confirmed by in vivo investigations.

Sources: Technische Universität Darmstadt, AlphaGalileo Foundation.

Article adapted by medical news today from original press release.

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Technical University Darmstadt (2011, September 9). New substances accelerate drug transport into cells. Medical news today. Retrieved September 9, 2011 from http://www.medicalnewstoday.com/releases/234124.php MLA
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