Small molecules can be linked to much larger cargoes and deliver them into a variety of cell types, according to an article to be published online in Nature Methods.
Cells tightly regulate which molecules they allow to enter, but it is often useful for research or therapeutic purposes to induce the uptake of bulky proteins or hydrophilic molecules, which are normally denied entry. It has been known for some time that certain short alpha-helical peptides can permeate the cell membrane; however, their application is hindered by high cost and the potential for biodegradation. David Selwood and colleagues now overcome these obstacles by designing small molecules based on this alpha-helical structure. These new small molecule carriers efficiently transport molecules that are typically denied entry such as dye molecules and proteins into several different cell types. With this report, Selwood and colleagues have introduced a novel strategy for intracellular delivery that could have wide-reaching implications for both basic research and pharmacology, including drug discovery and gene therapy. In an accompanying News & Views piece, Alain Prochiantz notes that this work may lead to the "the discovery of [other small molecule] mimics and to the development of efficient strategies to reach intracellular targets." Author contact: David Selwood (University College London, UK) E-mail: d.selwood@ucl.ac.uk Additional contact for comment on paper: Alain Prochiantz (Ecole normale supérieure, France) E-mail: prochian@biologie.ens.fr Abstract available online. (C) Nature Methods press release.
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