Reagent cuts peptide bonds
Peptide amide bonds are notoriously unreactive under physiological conditions, but Nenad M. Kostic and coworkers at Iowa State University, Ames, have now devised a reagent that cleaves peptides at pH 7 in a sequence-specific manner [J. Am. Chem. Soc., published online Dec. 24, 2003]. The reagent (shown, red) is a conjugate of a palladium(II) aqua complex, which cleaves amide bonds involving proline residues, and -cyclodextrin, which binds aromatic side chains and positions the inorganic complex for specific cleavage adjacent to a proline-phenylalanine sequence in a chosen peptide. The hydrolysis is fairly slow but could be improved. "Our ultimate goal is to complement natural proteolytic enzymes with synthetic inorganic-organic conjugates that have selectivities unachievable with natural enzymes," Kosti says. In a related study, the site-selective hydrolysis of proteins with synthetic catalysts under physiological conditions was also recently achieved by chemistry professor Junghun Suh and coworkers at Seoul National University, Korea [J. Am. Chem. Soc., 125, 14580, 2003].
Structure of peptide from amyloid fibril
In a study that reveals new details about the type of protein assemblies associated with Alzheimer's, Parkinson's, and transmissible spongiform encephalopathies such as mad cow disease, the first atomic-resolution structure of a peptide in an amyloid fibril has been obtained. Amyloid fibrils can't be crystallized, making crystallographic analysis impossible, and they're insoluble, so solution NMR can- not be used either. Therefore, Robert G. Griffin of MIT; Cait E. MacPhee of the University of Cambridge, in England; and coworkers used solid-state NMR to determine the structure of an 11-residue amyloid peptide from the protein transthyretin [Proc. Natl. Acad. Sci. USA, 101,711 (2004)]. Griffin says the structure was made possible by his group's development of novel NMR techniques for measuring distances and torsion angles in uniformly labeled biomolecules and by procedures developed by the Cambridge group for preparing well-ordered samples. The study could help lead to "a complete characterization of fibrils of more complex molecules, including the full-length biologically active compounds," comments Beat H. Meier of the Swiss Federal Institute of Technology, Zurich.
Robot reasons scientifically, experiments
"Robot scientist" conjures up an image of an androidlike contraption that does science and perhaps gives talks at meetings. But the robot scientist developed by computer science professor Ross D. King of the University of Wales, Aberystwyth, and his U.K. colleagues isn't anywhere near that sophisticated. Nevertheless, the PC-based benchtop system is capable of generating hypotheses, designing and carrying out experiments to test them, interpreting the data obtained, and then repeating the cycle [Nature,427, 247 (2004)]. The robot was given the problem of determining the function of certain genes in baker's yeast. Using "knockout" strains of yeast that have had one gene removed, the robot performed microtiter growth experiments that allowed it to "discover" the functions of genes that the scientists already knew about. In one key measure, no significant difference was seen between the robot's performance and the best that a group of humans could do. "We now plan to extend the system to be able to uncover the function of genes whose role is currently unknown," the team writes. After that, they hope to apply the robot scientist to drug design.
'Ice cream' gene identified
Guar gum and locust bean gum are polysaccharides that are added to ice cream, shampoo, paper, and cement as texturizing and thickening agents. They are galactomannans--copolymers of galactose and mannose--produced by plants to provide energy storage for seeds and, along with cellulose, to support cell walls. A research team led by Kanwarpal S. Dhugga of Pioneer Hi-Bred International, Johnston, Iowa, and coworkers has now identified the gene for an enzyme that completes the biochemical pathway that plants use to synthesize galactomannans [Science, 303,363 (2004)]. Designated CtManS, the gene codes for the mannan synthase enzyme that makes the -1,4-mannan backbone of guar galactomannan. Another enzyme, -galactosyltransferase, whose gene has previously been identified, then adds galactosyl residues to the mannan backbone. After isolating the CtManS gene, the team identified and confirmed its activity by transforming it into soybean cell cultures followed by biochemical assays and immunochemistry. The work could lead to a less expensive method to produce galactomannan gums by genetically modifying high-yield crops such as soybeans.
Self-assembly of nanorods
The self-assembly of two- and three-component nanorods into higher ordered structures can be predictably controlled by varying the relative lengths of the rods' gold and hydrophobic polymer components, reports a group from Northwestern University [Science, 303, 348 (2004)]. The group, led by chemistry professor Chad A. Mirkin, likens the two-component nanorods to small cones because the gold portion's diameter is larger than that of the polymer portion. When hydrophobic interactions bring the nanorods' polymer portions together during self-assembly, this difference in diameter gives the assembled structures a distinctive curve. The longer the gold portion is in relation to the polymer, the tighter the structure's curve. (The structure shown has a 1:4 gold-polymer ratio.) The group also made three-component gold-polymer-gold rods. These act like cylinders, rather than cones, and self-assemble into flat sheets. According to Mirkin, the alumina template that is used to synthesize the nanorods plays a critical role by prealigning the rods in a way that facilitates their self-assembly.