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New substances accelerate drug transport into cells

Date:
September 8, 2011
Source:
Technische Universität Darmstadt
Summary:
Biologists 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.

Biologists at the Technische Universität 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.

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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. Herce, of the TU‑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 international journal Nature Communications, 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 time lags until drugs begin to exhibit their effects might be 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 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 transporters, 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 kept under artificial conditions, will be confirmed by in vivo investigations.


Story Source:

The above story is based on materials provided by Technische Universität Darmstadt. Note: Materials may be edited for content and length.


Journal Reference:

  1. Gisela Lättig-Tünnemann, Manuel Prinz, Daniel Hoffmann, Joachim Behlke, Caroline Palm-Apergi, Ingo Morano, Henry D. Herce, M. Cristina Cardoso. Backbone rigidity and static presentation of guanidinium groups increases cellular uptake of arginine-rich cell-penetrating peptides. Nature Communications, 2011; 2: 453 DOI: 10.1038/ncomms1459

Cite This Page:

Technische Universität Darmstadt. "New substances accelerate drug transport into cells." ScienceDaily. ScienceDaily, 8 September 2011. <www.sciencedaily.com/releases/2011/09/110907075759.htm>.
Technische Universität Darmstadt. (2011, September 8). New substances accelerate drug transport into cells. ScienceDaily. Retrieved October 30, 2014 from www.sciencedaily.com/releases/2011/09/110907075759.htm
Technische Universität Darmstadt. "New substances accelerate drug transport into cells." ScienceDaily. www.sciencedaily.com/releases/2011/09/110907075759.htm (accessed October 30, 2014).

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