science/ technology concentrates concentrates
Static loops control size of DNA toroids Properly controlled collapse of DNA chains into compact particles (conden sation) could provide nonviral alterna tives for gene therapy, according to Nicholas V. Hud, a biochemist at Geor gia Institute of Technology, and collabo rators M. Richard Shen and Rod Balhorn at Lawrence Livermore National Laboratory and Kenneth H. Downing at Lawrence Berkeley National Laborato ry. The researchers control the size of toroids formed during DNA condensa tion by inserting static loops in the DNA [/. Am. Chem. Soc, 122, 4833 (2000)]. The loops are formed by multiple Α-tracts, which are six consecutive ade nine residues that produce a bend of around 20° in double-stranded DNA. When observed within five minutes of initiating condensation, DNA contain ing the loops forms toroids with an out er diameter of about 45 nm. Without the loops, the toroids have an outer diame ter of about 130 nm. However, the small er toroids aggregate within 30 minutes, suggesting that the smaller structures could be in a metastable state. Further studies are under way using loops of various sizes to determine what ulti mately dictates the size of the toroids.^
mor cells, including administering anti bodies to either RAGE or amphoterin and introducing defective forms of RAGE into the cells. In all cases, the treatment signif icantly inhibited the growth, movement, and local invasion of tumor cells as well as their metastasis to the lungs. The ef fect seems to be linked to activity of the MAP kinase family of signal transduction effector molecules. The RAGE-amphoterin pathway is a promising target for new anticancer drugs, the researchers suggest.^
Polymer sandwiches with different fillings
For years, chemists learning the ins and outs of "crystal engineering" have known how to prepare layered crystals consisting of organic polymeric sheets interspersed with other mole cules. Chemists 8 in Osaka, Japan, ™ have now gone one step fur ther by showing that the polymer sheets "can be separated from each other and then reassem!" bled into new polymer sand wiches with differentfillings,"according to chemical engineering and materials sci ence professor Michael D. Ward of the University of Minnesota, Minneapolis. Targeting protein pair Akikazu Matsumoto, associate profes can stop cancer spread sor of applied chemistry at Osaka City University, and colleagues create a crys The invasiveness, growth, and move tal lattice consisting of layers of mument of cancer cells can be blocked—in conate anions (reactive dienes with a mice, at least—by interfering with the in carboxylate group at either end) sand teraction of a pair of proteins, according wiched between layers of alkylammonito a U.S.-Japanese research team headed um cations [Nature, 4 0 5 , 328 (2000)]. by Ann Marie Schmidt, associate profes When exposed to ultraviolet light, the sor of surgery at Columbia University muconate anions in each layer polymer [Nature, 4 0 5 , 354 (2000)]. One element ize to generate a molecule-thick poly of the pair is a receptor found on the sur mer sheet (shown in green). Exposing face of many cells called RAGE (receptor this "synthetic clay" to acid removes for advanced glycation end products) ; the the alkylammonium cations (blue) and other is one of the receptor's many li- frees the uncharged polymer sheets. gands, a protein called amphoterin. Earli "Remarkably," Ward writes in a Nature er work had shown that this ligand and commentary, "these free sheets can be receptor work together during embryon joined together again using any one of a ic development to help the tips of neu number of alkylammonium ions, which rons spread and grow, so the researchers serve as a molecular glue" and control reasoned that the protein pair might play the spacing between the sheets. Such a similar role for invading tumor cells. polymer crystals might be useful for They used several approaches to block molecular recognition, separations, and the ligand-receptor interaction in brain tu- catalysis.^ 34
MAY22,2000C&EN
lo volcano spews S 2 gas The plume spewing from the volcano Pele on Jupiter's moon lo contains gas eous diatomic sulfur in addition to sulfur dioxide gas, observations by the Hubble Space Telescope indicate [Science, 288, 1208 (2000)]. Astronomer John R Spen cer of Lowell Observatory in Flagstaff, Ariz., and coworkers observed the plume in October 1999, just as the Galileo space craft was flying by. They used Hubble's imaging spectrograph to obtain spectra of the plume at wavelengths of 180 to 310 nm against the background of Jupi ter. Their analysis suggests the ratio of S0 2 to S2 in the plume is between 3 and 12. The relatively high ratio confirms the conclusion reached by other researchers that Io's interior is free of metallic iron near the surface. Diatomic sulfur is unsta ble to UV light and has been detected in only two other astronomical contexts, the researchers note: in comae near the nucle us of comets and at the sites where pieces of comet Shoemaker-Levy plunged into Ju piter. Decomposition of S2 by UV photoly sis and subsequent polymerization to red S3 and S4 molecules could account for the red color of Pele's plume deposits.^
Dual solubility of toxic herbal compounds In a study that could lead to the mecha nism of action of toxic compounds found in some traditional herbal teas and medi cines, an international team has de scribed for the first time the molecular forms these compounds adopt in solu tion. Otonecine-type pyrrolidine alka loids (OTPAs)—naturally occurring hepatotoxic compounds found in a wide vari ety of plants, including some used to make herbal products—are soluble in both organic and aqueous media. Their water solubility may lead to their relative ly high levels in herbal preparations such as comfrey tea. And their lipid solubility may enhance their absorption in the body after ingestion. Associate professor of pharmacology Ge Lin of the Chinese Uni versity of Hong Kong and coworkers from Canada and China have now shown, using NMR spectroscopy, that two repre sentative OTPAs—clivorine and ligularine—exist in a nonionized form in or ganic solution but adopt an ionized state in water, explaining how they exhibit dual solubility \J. Nat. Prod., published April 20 ASAP, http://pubs.acs.org/ journals/jnprdf/] .
