April 30 , 2008
International team of researchers explain how birds navigate

Upon excitation with light, an electron moves from one end of the molecule to the other. The time it takes for this electron to return to its initial position is sensitive to the magnitude and direction of magnetic fields similar to those of the Earth. Birds may use a similar phenomenon to navigate.

It has long been known that birds and many other animals including turtles, salamanders and lobsters, use the Earth’s magnetic field to navigate, but the nature of their global positioning systems (GPS) has not been completely understood.

One school of thought hypothesizes that birds use magnetically-sensitive chemical reactions initiated by light (called chemical magnetoreception) to orient themselves, but no chemical reaction in the laboratory, until now, has been shown to respond to magnetic fields as weak as the Earth’s.

Scientists from Arizona State University and the University of Oxford, whose work appears in the April 30 advanced online publication of the journal Nature, have synthesized and studied a sophisticated molecule that, under illumination, is sensitive to both the magnitude and the direction of magnetic fields as tiny as the Earth’s, which is, on average, one-twenty thousandth as strong as a refrigerator magnet.

ASU’s Devens Gust, professor of chemistry and biochemistry in the College of Liberal Arts and Sciences, states that “although the chemical magnetoreception mechanism for avian magnetic navigation has been discussed by many investigators, our research provides the first proof that this mechanism can actually function with magnetic fields as small as those of the Earth.”

"Chemical compass model of avian magnetoreception", Kiminori Maeda, Kevin B. Henbest, Filippo Cintolesi, Ilya Kuprov, Christopher T. Rodgers, Paul A. Liddell, Devens Gust, Christiane R. Timmel& P. J. Hore, Nature (30 Apr 2008), doi: 10.1038/nature06834.

Link to abstract

Full story from ASU News

April 25, 2008
Fromme and Thorpe Groups Develop new technique for fitting cryo EM Maps of Proteins

Recent experimental advances in producing density maps from cryo-electron microscopy (cryo-EM) have challenged theorists to develop improved techniques to provide structural models that are consistent with the data and that preserve all the local stereochemistry associated with the biomolecule. The Fromme and Thorpe groups have developed a new technique that maintains the local geometry and chemistry at each stage of the fitting procedure. They show that by incorporating the correct local stereochemistry in the modeling, structures can be obtained with effective resolution that is significantly higher than might be expected from nominal cryo-EM resolution.

Their research was depicted on a recent cover of the Biophysical Journal: " Fitting Low-Resolution Cryo-EM Maps of Proteins Using Constrained Geometric Simulations ", Craig C. Jolley, Stephen A. Wells, Petra Fromme, and M. F. Thorpe Biophysical Journal, 94, 2008, pp 1613–1621

Link to abstract , Link to Cover Story

April 18, 2008
David LeBard and Dmitry Matyushov find Gigantic Reorganization Energy of Electron Transfer for a Hydrated Metalloprotein

When people think about about the transport of electrons in biological energy chains they turn their attention to redox potentials and Gibbs energies to find energetically downhill pathways. In order to access the activation energy, one also needs an additional energy called the reorganization energy of the hydrating water and the protein. Two novel characteristics of the problem came from recent extensive Molecular Dynamics simulations of the photosynthetic redox protein plastocyanin. First, it was found that the breadth of electrostatic fluctuations created by hydrating water far exceeds all previous estimates and results in a gigantic reorganization energy. Second, it was found that the spectrum of relaxation times is so wide that most biological electron transitions find themselves in non-ergodic regime when some parts of the fluctuation spectrum are dynamically frozen. This finding suggests a possibility that nature plays with both the Gibbs energies and relaxation time-scales in optimizing its energy chains.

The results were reported in the recent issue of the J. Phys. Chem. B

"Glassy Protein Dynamics and Gigantic Solvent Reorganization Energy of Plastocyanin", David N. LeBard and Dmitry V. Matyushov, J. Phys. Chem. B, 112 (16), 5218 -5227, 2008. 10.1021/jp709586e S1520-6106(70)09586-X

Link to abstract , Link to full text

April 14, 2008
Richert group turns the table on liquid studies

When we use a mercury thermometer to monitor a baby's fever we are taking advantage of the way temperature changes the liquid's density. We flow heat into the liquid by collisions with the molecules of a hotter body, and the liquid responds by changing its "molecular configuration" to one with lower density.

Most measurements of temperature effects on materials are made this way... But not all. Ranko Richert's research group has found a way to change the configuration first. It is likely that this is the way the ARMY's recently developed "active denial" non-lethal defence system also works.

"It is a new way of thinking about liquids," adds Regents' Professor Austen Angell. " I think people will take a lot of notice of this development." Richert's results were reported in the physic's community's top journal Physical Review Letters.

"Measuring the Configurational Heat Capacity of Liquids", L.-M. Wang, R. Richert, Phys. Rev. Lett. 99, 185701 (2007).
Abstract: A high electric field impedance experiment on supercooled molecular liquids is employed to transfer energy to the slow modes by absorption from the field and detect the increase of their 'configurational temperature', Tcfg, via the change of the relaxation times. This allows us to determine the configurational heat capacity, which accounts for most of the excess heat capacity for stronger liquids, but for only half of the heat capacity step in the case of more fragile systems. It is also observed that Tcfg gradually approaches the phonon temperature on the structural relaxation time scale.

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April 7, 2008
Mark Hayes and colleagues are making progress with their small scale proteomics research

One of the major challenges in developing personalized medicine is analyzing the stunningly complex mixture of biomolecules in typical human fluid samples-some estimate as much as a million different chemical species. The revolution in micro and nanoscale fabrication and understanding has begun to allow new strategies to be developed. One shown here uses a micro and nanoscaled surface (designed after the self-cleaning 'Lotus Leave') combined with a separations technique to divide proteins within a single droplet for further processing. The use of 'digital magnetofluidics' and 'within-droplet separations' are both unique capabilities and the combination of them provides a powerful new tool to analyze complex biological mixtures more effectively.

The work is centered in Tony Garcia's lab at Harrington Department of Bioengineering, Arizona State University with the collaboration between Ana Egatz*, Antonio A. Garcia*&**, Mark Hayes**, Sonia Melle***, Miguel Angle Rubio****, Nicole Zwick**, Melissa Mclauchlin**, and Manuel Marquez*.

*Harrington Department of Bioengineering, Arizona State University, ** Department of Chemistry and Biochemistry, Arizona State university, ***Universidad Complutense de Madrid, ****Universidad Nacional de Educacion a Distancia.

April 1, 2008
Discovery of Quinolinediones Exhibiting a Heat Shock Response and Angiogenesis Inhibition

A series of substituted quinoline-5, 8-diones were synthesized and evaluated as inhibitors of the chaperone protein Hsp90 using two assays: competition for binding to C-terminal ATP-binding site and competition for binding to N-terminal ATP-binding site. In addition, the ability of the compounds to induce the heat shock response was determined using a reporter fibroblast cell line. Of all the compounds assayed, only 6-aziridinyl-2-biphenylquinoline-5, 8-dione induced a heat shock response and did so without interacting at the ATP binding sites of Hsp90. COMPARE analysis was carried out on quinoline-5, 8-diones active in the National Cancer Institute's 60-cell line screen with the goal of discovering quinoline-5, 8-dione structures that interact with other cellular targets (molecular targets) important for cancer chemotherapy. COMPARE analysis led to the discovery of a combretastatin-like quinoline-5, 8-dione structure that in fact inhibited angiogenesis.

"Discovery of Quinolinediones Exhibiting a Heat Shock Response and Angiogenesis Inhibition ", Robert H. J. Hargreaves, Cynthia L. David, Luke J. Whitesell,§ Daniel V. LaBarbera,† Akmal Jamil, Jean C. Chapuis, and Edward B. Skibo, J. Med. Chem., ASAP Article, 10.1021/jm7014099

Link to abstract

March 25, 2008
Dielectrophoretic manipulation of DNA: Separation and polarizability

New faculty member Alexandra Ros and coworkers from Bielefeld University (Germany) have demonstrated the first example of DNA separation based on dielectrophoresis. Although the separation of polymers based on the combination of dielectrophoretic trapping and electrophoretic forces was proposed 15 years ago, the experimental realization had not been reported.

They addressed this problem for long DNA fragments in a simple and easy-to-fabricate microfluidic device in which the DNA is manipulated by electrophoresis and by electrodeless dielectrophoresis. By slowly increasing the strength of the dielectrophoretic traps in the course of the separation experiments, they were able to perform efficient and fast DNA separation according to length for two different DNA conformations: linear and supercoiled covalently closed circular (ccc) plasmid DNA. The underlying migration mechanism - a thermally induced escape process out of the dielectrophoretic traps in the direction of the electrophoretic force - is sensitive to different DNA fragments due to the length-dependent DNA polarizability. The migration mechanism is also exploited for the quantitative measurement of the DNA polarizability. This new and simple technique opens way to a systematic characterization of the polarizability not only for DNA with respect to its length-dependence, but also for other biomolecules, such as proteins, and also with respect to other molecular properties, such as conformation. These results have further direct implications to future biotechnological applications like gene therapy and DNA vaccination.

"Dielectrophoretic manipulation of DNA: Separation and polarizability", J. Regtmeier, T. T. Duong, R. Eichhorn, D. Anselmetti, A. Ros, , Analytical Chemistry, 79, 3925-3932, (2007).

Link to abstract

March 3, 2008
Meteorite molecules mirror those on Earth  

Courtesy of Linda Welzenbach, Smithsonian Institution, and the Antarctic Search for Meteorites Program

An important discovery has been made with respect to the mystery of “handedness” in biomolecules. Researchers led by Sandra Pizzarello, a research professor at Arizona State University, found that some of the possible abiotic precursors to the origin of life on Earth have been shown to carry “handedness” in a larger number than previously thought.

The work is being published in this week’s Proceedings of the National Academy of Sciences (PNAS). The paper is titled, “Molecular asymmetry in extraterrestrial chemistry: Insights from a pristine meteorite,” and is co-authored by Pizzarello and Yongsong Huang and Marcelo Alexandre, of Brown University.

Pizzarello, in ASU’s Department of Chemistry and Biochemistry, worked with Huang and Alexandre in studying the organic materials of a special group of meteorites that contain among a variety of compounds, amino acids that have identical counterparts in terrestrial biomolecules. These meteorites are fragments of asteroids that are about the same age as the solar system (roughly 4.5 billion years.) Scientists have long known that most compounds in living things exist in mirror-image forms. The two forms are like hands; one is a mirror reflection of the other. They are different, cannot be superimposed, yet identical in their parts. full story...

Link to abstract

Jan 29, 2008
Herckes group develops new methods for atmospheric detection of Hydrocarbons

The Herckes group in collaboration with researchers at the University of Strasbourg have developed new methods to determine oxygenated (oxy-PAH) and nitrated polyaromatic hydrocarbons (nitro-PAH) in the atmosphere. These pollutants can be emitted directly into the atmosphere through combustion processes or formed in situ through photo oxidation. They are of particular interest due to their high toxicity and carcinogenicity. The manuscripts describe new methods using liquid chromatography with online derivatisation and fluorescence detection respectively liquid chromatography with tandem mass spectrometry to detect and quantify these species. These techniques will be instrumental for atmospheric occurrence studies. The manuscripts also report first ambient data on these species in atmospheric particulate matter in Tempe (AZ) and Strasbourg (France).

"Determination of oxygenated polycyclic aromatic hydrocarbons in atmospheric aerosol samples by liquid chromatography–tandem mass spectrometry ", O. Delhomme, M. Millet, P. Herckes, Talanta, 74, 703-710, 2008.

Link to abstract

"Post-column derivatisation of nitro-polycyclic aromatic hydrocarbons for their analysis by HPLC fluorescence. Application to atmospheric aerosols", O. Delhomme, P. Herckes, M. Millet, Analytical and Bioanalytical Chemistry, 389, 1953-1959, 2007.

Link to abstract

Jan. 10, 2008
Nanotechnology innovation may revolutionize gene detection in a single cell

Hao Yan and his research group have developed the world’s first gene detection platform made up entirely from self-assembled DNA nanostructures. The results, appearing in the January 11 issue of the journal Science, could have broad implications for gene chip technology and may also revolutionize the way in which gene expression is analyzed in a single cell.

"Self-Assembled Water-Soluble Nucleic Acid Probe Tiles for Label-Free RNA Hybridization Assays", Yonggang Ke, Stuart Lindsay, Yung Chang, Yan Liu,, Hao Yan. Science 11 January 2008: Vol. 319. no. 5860, pp. 180 - 183.

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Dec. 12, 2007
In Vitro Selection of Histone H4 Aptamers for Recognition Imaging Microscopy

In a recent issue of the Journal of the American Chemical Society, Chaput and Lindsay report the in vitro selection and evaluation of histone H4 aptamers as affinity reagents in the atomic force microscopy technique known as recognition imaging microscopy. In contrast to commercial antibodies, the selected aptamers showed high binding affinity and selectivity, both in solution and on the cantilever tip of an atomic force microscopy. Their strategy now opens up the possibility that aptamers could be used as antibody surrogates in studying key epigenetic modification involved in chromatin remodeling.

“In Vitro Selection of Histone H4 Aptamers for Recognition Imaging Microscopy”, Liyun Lin, Doris Hom, Stuart M. Lindsay, and John C. Chaput. J. Am. Chem. Soc. 129(2007), 14568-14569.

Link to abstract

Nov. 30, 2007
Permanent Electric DipoleMoment of Molybdenum Carbide

Understanding the nature of the transition metal/carbon bond is fundamental to many areas of organometallic chemistry and catalysis. The permanent electric dipole moment, μ_e, is the best gauge of the polarity of a chemical bond and a comparison of theoretical and experimentally derived values of μ_e is a primary means of assessing the quality of electronic structure calculation being developed to model properties of transition metal containing molecules. The need for this benchmark data on simple metal containing molecules has increased as electronic structure computational approaches have evolved from traditional high level ab initio methods to the current extensively implemented density functional theory (DFT) methods because the results of DFT predictions depend radically on the nature of both the functional and basis set employed. The Steimle lab has recently succeeded in experimentally determining μ_e of molybdenum monocarbide, MoC, and thus the polarity of this important metal carbide chemical bond. The experiment, which is unique to the ASU group, employs ultra-high resolution optical Stark spectroscopy of molecular beam samples. A manuscript describing the results was recently accepted for publication in the Journal of Chemical Physics.

“Permanent Electric DipoleMoment of Molybdenum Carbide”, H. Wang, W.L. Virgo, J. Ven, and T. C. Steimle, J. Chem. Physics Vol 127, 124302 (2007).

Link to abstract

Nov. 15, 2007
Synthetic hydrogenases: Incorporation of an iron carbonyl thiolate into a designed peptide

Hydrogen is one of the leading contenders for fuel of the future, and cheap, renewable catalysts for its production are highly sought after. Although typical industrial catalysts utilize precious metals such as platinum, hydrogenases, the biological catalysts for the reversible oxidation of hydrogen, utilize the base metal iron. However, unraveling the fundamental mechanism of the catalysis of biological hydrogen production has not proven easy. Classically, two approaches have been taken: study of the intact enzymes and synthesis of small inorganic model systems. While significant progress has been made, both methods have left many questions unanswered and a need for new tactics exists.

In a recent publication, Jones and coworkers are offering a new alternative. They have constructed the first intermediate sized model system incorporating features of both the inorganic active site and the protein scaffold. The synthesis and characterization of a de novo designed peptide incorporating an iron carbonyl thioloate mimic of the [FeFe]-hydrogenase active site, the first generation of peptide-based, artificial hydrogenases, are described. This peptide and the reaction with cysteine used for creation of the metallocluster within it open the door for future generations of artificial hydrogenases. These artificial proteins will prove to be invaluable tools for testing hypotheses regarding hydrogenase biosynthesis and mechanism as well as platforms for design of novel, artificial redox catalysts.

"Synthetic hydrogenases: Incorporation of an iron carbonyl thiolate into a designed peptide", A. K. Jones, B. R. Lichtenstein, A. Dutta, G. Gordon, and P. L. Dutton, J. Am. Chem. Soc., 129 (2007).

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Nov. 7, 2007
Enzyme activity at the flick of a switch

Joseph Wang and co-workers have used a combination of nanowires and nanotubes to create a switchable bioelectronic device for the on-demand transformation of alcohols to aldehydes.

Wang's system uses nickel-gold nanowires, which have an enzyme trapped halfway along them, in combination with an electrode coated with carbon nanotubes. The orientation of the nanowires in the device can be switched from vertical to horizontal by a magnetic field.

In the horizontal position, contact between the enzyme and the electrode allows the enzyme - in this case alcohol dehydrogenase (ADH) - to catalyse the transformation of ethanol to acetaldehyde. Regeneration of the enzyme's cofactor (NAD⁺) by the nanotube surface maintains the catalytic activity, and allows analysis by electrochemical methods. This means the device could be used as an alcohol sensor.

When the nanowires are switched to the vertical position, the reaction is inhibited because the enzyme has no contact with the electrode.  Wang says this switchability could hold great promise for regulating the operation of biofuel cells or bioreactors.

Frederic Barriere, an expert in bioelectrochemistry at the University of Rennes, France, sees of the advantages of Wang's system over established methods. 'The oxidation of NADH on traditional electrodes quickly fails because of adsorption and surface fouling. The use of electrodes coated with acid-purified carbon nanotubes avoids this problem,' said Barriere.

"Adaptive nanowire–nanotube bioelectronic system for on-demand bioelectrocatalytic transformations", Rawiwan Laocharoensuk, Andrea Bulbarello, Saverio Mannino and Joseph Wang, Chem. Commun., 2007, 3362 - 3364, DOI: 10.1039/b708313k

Link to abstract

Oct. 31, 2007
Ranko Richert's article featured on the ACS Publications web as a "Hot Paper"
Solvation Dynamics and Electric Field Relaxation in an Imidazolium-PF₆ Ionic Liquid: from Room Temperature to the Glass Transition

Time-resolved phosphorescence spectra and anisotropy of quinoxaline were measured in an ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate (BMIM-HFP), in its supercooled state near the glass-transition temperature. The solvation dynamics results are compared with the rotational motion of the probe and with the dielectric behavior of the neat ionic liquid. The dynamics in the viscous state are highly dispersive and show a super-Arrhenius temperature dependence, as typical for glass-forming materials. Combined with room-temperature results, solvation dynamics is observed to follow the structural relaxation times in terms of /T for more than 10 decades, from subnanoseconds at room temperature to seconds near the glass-transition temperature Tg. The dielectric modulus relaxation follows this trend only for temperatures T > 1.2Tg and departs significantly from /T in the 1.1Tg > T > Tg range. This deviation is reminiscent of the enhanced translational diffusion or fractional Stokes-Einstein behavior observed in many fragile supercooled liquids. Because the electric field relaxation in BMIM-HFP includes dc conductivity, this correlation function involves translational motion and thus displays the effect of enhanced diffusivity. A microscopic model is required for rationalizing the decoupling of solvation dynamics from the longitudinal time scales and the limitation of this effect to the viscous regime with T < 1.2Tg.

"Solvation Dynamics and Electric Field Relaxation in an Imidazolium-PF₆ Ionic Liquid: from Room Temperature to the Glass Transition", Naoki Ito and Ranko Richert, J. Phys. Chem. B, 111 (18), 5016 -5022, 2007.

Link to abstract

Oct. 23, 2007
Metal Turned to Glass

In order to form a glass by cooling a liquid, the normal process of solid crystallization must be bypassed. Achieving that for a pure metal had seemed impossible — until pressure was applied to liquid germanium. In Yarger , Angell and their research team's new paper published in Nature, another member has been added to the ubiquitous family of materials: a glass made by cooling a pure, ‘monatomic’ metal.

"Vitrification of a Monatomic Metallic Liquid", M. H. Bhat, V. Molinero, E. Soignard, V. C. Solomon, S. Sastry, J. L. Yarger& C. A. Angell, Nature 448, 787-790 (2007).

Link to abstract

Oct. 16, 2007
Experimental Evidence That GNA and TNA Were Not Sequential Polymers in the Prebiotic Evolution of RNA

In this month’s issue of the Journal of Molecular Evolution, Chaput and coworkers demonstrate that glycerol nucleic acid (GNA) and threose nucleic acid (TNA) were not consecutive biopolymers in the same evolutionary pathway that gave rise to RNA in a hypothetical RNA world. Coupled with their chemical simplicity, polymers for both systems are known to form stable Watson-Crick duplex structures with themselves and RNA, thereby providing a possible mechanism for the transfer of genetic information between successive genetic systems. Using chemical synthesis and molecular biology, the Chaput lab demonstrated that complementary GNA and TNA polymers are unable, even after prolonged incubation times, to adopt stable helical structures by intersystem cross-pairing. This experimental observation suggests that GNA and TNA, whose structures derive from one another, were not consecutive polymers in the same evolutionary pathway to RNA—a result that provides new constraints on models that describe the evolution of early genetic systems.

"Experimental Evidence That GNA and TNA Were Not Sequential Polymers in the Prebiotic Evolution of RNA", Ying-Wei Yang, Su Zhang, Elizabeth O. McCullum, and John C. Chaput. J. Mol. Evol. 2007, 65, 289–295.  

Link to abstract

Oct. 9, 2007

Anbar and members of his group are involved in two new studies that provide evidence of the presence of O₂ in the atmosphere tens of millions years before the Great Oxidation Event. This event, which began around 2.4 billion years ago, marked the Earth’s irreversible transition to an oxygenated world that can support complex life. The detailed cause of this event is unknown. The two studies were published in the Sept. 28 issue of Science.

The researchers analyzed samples of 2.5 billion year old seafloor obtained for the study by subsurface drilling in Western Australia. A team led by Anbar examined the amounts of the trace metals molybdenum, rhenium and uranium using ICP mass spectrometry (more). The presence of these elements in oceans and ocean sediments depends on the oxidation state of the environment. Another group, led by Alan J. Kaufman at the University of Maryland, focused on sulfur isotope variations that are also sensitive to O₂abundance (more). Both groups found unexpected, correlated changes that suggest the presence of small but significant amounts of O₂ in the environment 2.5 billion years ago, and a shift from lower O₂ abundance prior to that time. These two lines of evidence strengthen the notion that organisms began producing O₂ long before the Great Oxidation Event, and hence that the rise of O₂ in the atmosphere was ultimately controlled by geological processes that prevented biologically-produced O₂ from accumulating in the atmosphere before that time.

This research was supported by major grants from NASA and the National Science Foundation.

Link to abstracts:
http://www.sciencemag.org/cgi/content/abstract/317/5846/1900?etoc,
http://www.sciencemag.org/cgi/content/abstract/317/5846/1903?etoc

Oct. 2, 2007
LDA “double-counting” energy expression

The LDA+U method has been around for about two decades, as the most popular way in investigation of strongly-correlated electron systems such as high-Tc superconductors, colossal magneoresistance oxides and heavy fermions. By critically examining the LDA+U method regarding its self-interaction correction of the LDA, the Seo group has derived an LDA “double-counting” energy expression which led to a more reasonable self-interaction correction in an alternative LDA+U scheme (Self-interaction correction in the LDA+U method, PHYSICAL REVIEW B 76, 033102, 2007). The new method is based on the previous work of the Seo group that resulted in a unified theory of magnetic exchange interactions in various magnetic materials (Density functional perturbational orbital theory of spin polarization in electronic systems. I. Formalism, THE JOURNAL OF CHEMICAL PHYSICS 125, 154105, 2006). It is anticipated that the new method correctly predicts the magnetic ground states of the strongly-correlated electron systems in first principle electronic band structure calculations and is currently implemented by physicists in Leibniz Institute for Solid State and Materials Research in Dresden, Germany.

Link to abstract

Sep. 24, 2007
Fluorescence Properties and Photophysics of the Sulfoindocyanine Cy3 Linked Covalently to DNA

The Levitus lab has undertaken an extensive study of the photophysical and fluorescence properties of Cy3, one of the most popular fluorescent dyes used in biophysical and biological applications. In particular, the team concentrated on elucidating how these properties depend on the local environment of the dye when it is attached to DNA. The authors demonstrated that specific interactions between the dye and DNA are responsible for dramatic changes in its fluorescence efficiency (‘brightness’). These interactions also affect the local mobility of the probe, complicating the analysis of experiments where Cy3 is used as the donor in a FRET pair. The remarkable variations in the photophysical properties of Cy3-DNA constructs demonstrate that caution should be used when Cy3 is used in studies employing DNA conjugates. This is particularly critical when this dye is used to probe conformational dynamics in nucleic acids or DNA-protein interactions. This work was recently published in J. Phys. Chem. B, the most cited journal in Physical Chemistry.

"Fluorescence Properties and Photophysics of the Sulfoindocyanine Cy3 Linked Covalently to DNA" Matthew E. Sanborn, Brian K. Connolly, Kaushik Gurunathan, and Marcia Levitus. J. Phys. Chem. B, 111 (37), 11064 -11074, 2007 

Link to abstract

Sep. 18, 2007
Spatially Addressable Multiprotein Nanoarrays Templated by Aptamer-Tagged DNA Nanoarchitectures

The Yan lab has constructed, using a self-assembly approach, arrays of multiple proteins onto rigid DNA nano-scaffolds. In this work, self-assembled DNA tiles were designed to bear protein-binding nucleic acid loops, known as aptamers, at defined positions. The authors demonstrated that proteins can be organized into well-defined geometric patterns with accurate control of the protein placement at nanometer scale. Such protein nanoarrays could be used to investigate distance dependent biomolecular interactions, with applications in medical diagnostics. This work was recently published in J. Am. Chem. Soc. [ Chhabra, R.; Sharma, J.; Ke, Y.; Liu, Y.; Rinker, S.; Lindsay, S.; Yan, H., Spatially Addressable Multiprotein Nanoarrays Templated by Aptamer-Tagged DNA Nanoarchitectures. J. Am. Chem. Soc.129, 10304-10305 ( 2007 )] and highlighted in Nature Nanotechnology. http://www.nature.com/nnano/reshigh/2007/0807/full/nnano.2007.287.html

Link to abstract

Sep. 12, 2007
Mutations in telomerase genes linked to hereditary lung disease

The Chen lab together with researchers at Johns Hopkins University have discovered an important genetic link in a hereditary form of a fatal lung disease, idiopathic pulmonary fibrosis (IPF) which affects more than 50,000 Americans annually.

The ends of human chromosomes are normally capped by special DNA-protein complexes, called telomeres, that consist of repetitive DNA and associated proteins. Telomerase is the key enzyme that maintains the integrity of the telomere caps. In this study, mutations in two of the telomerase genes, telomerase reverse transcriptase (TERT) and telomerase RNA (TR), were found in six families that suffered from inherited IPF. Further analyses showed that these telomerase gene mutations resulted in a reduction of telomerase enzyme activity and shortening of telomere length, which has been shown to cause cell death. This finding provides a target for genetic testing and hopefully gene therapy in the future.

The work is published in the March 29, 2007 issue of the New England Journal of Medicine, the #1 journal in medicine with an impact factor of 51.296.

“Telomerase mutations in families with idiopathic pulmonary fibrosis,” M. Armanios, J.L. Chen, W.E. Lawson, J.K. Alder, R.G. Ingersoll, C. Markin, M. Xie, J. Cogan, J.A. Philips III, P.M. Lansdorp, C.W. Greider and J.E. Loyd, New England Journal of Medicine 356 1317-1326 (2007).

Link to abstract

Sep. 4, 2007
X-ray Structure of Cerulean GFP: A Tryptophan-Based Chromophore Useful for Fluorescence Lifetime Imaging

Wachter and coworkers have recently discovered a pH-dependent conformational switch with optical read-out in an engineered cyan fluorescent protein that bears an indole-based fluorophore. The observed optical modulation may be related to photo-switching events that involve cis-trans isomerization of the spontaneously formed intrinsic chromophore.

Cyan fluorescent proteins belong to a group of proteins that are genetically encodable fluorescent markers widely used for in vivo labeling applications in biomedical research. In the present work, Wachter and co-workers provide a structural rational for the enhanced fluorescence properties of Cerulean GFP, a cyan fluorescent protein that was rationally engineered to be useful in non-invasive live tissue imaging techniques such as FRET (Förster resonance energy transfer) and FLIM (fluorescence lifetime imaging).

This work is published as an ACCELERATED PUBLICATION in the September 4 issue of the journal Biochemistry Volume 46, and will be featured as a "2007 HOT ARTICLE" by the journal, see link below. http://pubs3.acs.org/acs/journals/hot_article.menu?in_coden=bichaw

"X-ray Structure of Cerulean GFP: A Tryptophan-Based Chromophore Useful for Fluorescence Lifetime Imaging," Malo, G. D., Pouwels, L. J., Wang, M., Weichsel, A., Montfort, W. R., Rizzo, M. A., Piston, D. W., Wachter, R. M., Biochemistry (Accelerated Publication) 46 9865-9873 (2007).

Link to abstract

Aug. 27, 2007
Sweet entanglement: multivalent binding to sugar-coated gp120 is crucial for the anti-HIV activity of cyanovirin

The ability of attaching sugars to proteins, called glycosylation, is typical of eukaryotic cells. However, HIV and related viruses are able to hijack the host’s cellular enzymes to glycosylate their own surface proteins in an attempt to escape the host’s immune response to infection and facilitate viral transmission. The amino acid composition of a protein influences the type, level and pattern of glycosylation. Thus, the molecular signature of the glycans attached to the HIV envelope protein gp120 is unique and distinct from endogenous proteins, and constitutes an attractive target for novel antiviral compounds.

The Ghirlanda lab has recently discovered the molecular mechanism of action of a potent anti-HIV protein, cyanovirin, paving the way for the design of improved antiviral proteins. The findings are presented in a paper published on Biochemistry this month. In cyanovirin, the anti-HIV activity mediated by its high-affinity binding to oligosaccharides on the viral surface envelope protein gp120. The protein contains two carbohydrate-binding domains, A and B, each of which can bind short oligomannosides in vitro.

Until now, it was not clear whether the interaction with gp120 involved a single domain, or both domains simultaneously. The model could be further complicated complicated by the formation of a domain-swapped dimer form, in which part of each domain is exchanged between two monomers, which contains four functional carbohydrate-binding domains.

To clarify whether multivalent interactions with gp120 are necessary for the antiviral activity the group engineered a novel mutant, P51G-m4-CVN, in which the binding site on domain A has been knocked out; in addition, a P51G mutation prevents the formation of domain-swapped dimers under physiological conditions. The crystal structures at 1.8 Å of the free and of the dimannose-bound forms of P51G-m4-CVN, solved in collaboration with the Fromme group, reveals a monomeric structure in which only domain B is bound to dimannose. P51G-m4-CVN binds gp120 with affinity almost two orders of magnitude lower than wt-CV-N, and is completely inactive against HIV. The tight binding to gp120 is recovered in the domain-swapped version of P51G-m4-CVN, prepared under extreme conditions.

These findings demonstrate that the presence of at least two oligomannoside binding sites, either by the presence of intact domains A and B or by formation of domain-swapped dimers, is essential for activity.

Dr. Ghirlanda is designing novel antiviral agents based on the concept of multivalent interactions, by optimizing the oligomannose binding site to further improve its affinity, and by reengineering the protein to better control its oligomerization state.

"A Monovalent Mutant of Cyanovirin-N Provides Insight Into the Role of Multiple Interactions with gp120 for Antiviral Activity," R. Fromme, Z. Katiliene, F. Bogani, B. Giomarelli, T.Mori, J. McMahon, P. Fromme and G.Ghirlanda, Biochemistry 46 9199-9207 (2007).

Link to abstract