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Biological Chemistry


May 10, 2004 | APPEARED IN VOLUME 82, ISSUE 19


Polyamide clamp prevents nucleosome disassembly

A pyrrole-imidazole polyamide "clamp" that prevents nucleosomes from disassembling should be useful for studying the dynamics of these protein-DNA complexes during transcription and replication. As a space-saving measure, cells wrap their genomic DNA around protein beads to form nucleosomes, which are further packed to form chromatin. Cells must also have ways to transiently unpack DNA from nucleosomes, but the molecular details of how this might happen remain murky. Using X-ray crystallography, chemist Peter B. Dervan of Caltech, structural biologist Karolin Luger of Colorado State University, and coworkers show that a DNA-binding hairpin polyamide dimer (orange) can be used to tether the aligned minor grooves of DNA (space-filling model) that's been wrapped twice around the protein core of a nucleosome [Proc. Natl. Acad. Sci. USA, 101, 6864 (2004)]. Dervan and Luger hope to use such polyamide clamps to study nucleosome dynamics during transcription and replication and to target reagents or recruit proteins to specific nucleosomes

Polyglycerols block protein adsorption

Polyglycerols block protein adsorption Novel biocompatible polymeric materials that suppress the nonspecific adsorption of proteins are promising candidates as surface coatings for biomedical applications, according to chemists in Germany. Rainer Haag, professor of organic polymer chemistry at the University of Dortmund, and coworkers show that highly protein-resistant, self-assembled monolayers of dendritic polyglycerols on gold can be readily prepared by modifying the polymers with surface-active disulfide linker groups [Chem. Eur. J., 10, 2831 (2004)]. Polyglycerol monolayers are effective at blocking unwanted adsorption of proteins such as those used by bacteria and viruses to attach to surfaces, Haag observes. The new dendritic polyglycerol derivatives combine structural features of other protein-resistant materials; for example, hydrophilic surface groups and highly branched and flexible architectures. “Polyglycerol monolayers are as protein resistant as polyethylene glycol monolayers—the current benchmark for such materials,” Haag says. In addition, polyglycerol’s ability to withstand high temperatures and oxidation makes it a good candidate for coating medical devices that are heat-sterilized, he says.

Shining light on vitamin D biosynthesis

Sunlight shining on the skin generates vitamin D3. This compound is subsequently hydroxylated first at the carbon-25 position and then at the 1- position to create the main physiologically active form of the vitamin. These steps have been known for 30 years, but the identity of the enzyme that catalyzes the first hydroxyla-tion step has been shrouded in mystery. Now, a team led by David W. Russell, a molecular geneticist at the University of Texas Southwestern Medical Center, believes it has provided convincing evidence that a microsomal cytochrome P450 protein known as CYP2R1 is the enzyme in question [Proc. Natl. Acad. Sci. USA, published online May 5,]. In earlier work, the researchers proposed CYP2R1 as a likely candidate. Their current paper lends support to this hypothesis with genetic evidence from a patient lacking a functional version of CYP2R1. The patient, who had a mutation in his CYP2R1 genes that eliminated the protein’s ability to hydroxylate vitamin D3, had low plasma levels of 25-hydroxyvitamin D3 and symptoms of vitamin D deficiency.

Sensitive DNA detection without PCR

A particle-based assay based on “bio bar codes” can provide DNA detection comparable to the polymerase chain reaction without the need for enzymatic amplification [J. Am. Chem. Soc., 126, 5932 (2004)]. Chemistry professor Chad A. Mirkin and coworkers at Northwestern University describe an assay that relies on two types of particles with oligonucleotides on their surfaces. The team demonstrates the assay using the anthrax lethal factor gene as the target DNA. Gold nanoparticles are modified with DNA sequences complementary to a region of the target DNA and complementary to a bio bar code that identifies the particle. A magnetic iron oxide microparticle is modified with a second sequence complementary to the target DNA. The two particles sandwich the target DNA, and a magnetic field separates the sandwich from the sample. The bio bar code is then removed for analysis by a chip-based DNA detection method. The method is sensitive enough to detect DNA levels as low as 10 copies in the sample.


Growing nanotrees

Using gold nanoparticle “seeds,” researchers at Sweden’s Lund University have grown treelike nanowire structures (shown) out of GaP and other semiconducting materials [Nat. Mater., published online May 2,]. Solid-state physics professor Lars Samuelson and coworkers plant “nanoforests” by depositing catalytic nanoparticle seeds onto a substrate from which they grow nanowire “tree trunks” via a vapor-liquid-solid growth process. The researchers then repeat the process, depositing the seeds onto the tree trunks, in order to grow branches. They can also grow leaves onto the trees by repeating the process for a third time. The nano arborists say the seeding method gives them a high degree of control over the structures’ branch length, diameter, and number. They also can make structures in which the trunks, branches, and leaves are all made of different materials.



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