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Archive for the ‘Hot articles’ Category

HOT: Overcoming bacterial resistance to aminoglycoside antibiotics

04 Mar 2011

Aminoglycoside antibiotics are widely used in hospitals to treat serious and life-threatening infections. Because of their widespread use, bacterial resistance is becoming more of a problem and the search for aminoglycosides which are not affected grows ever more urgent.

Sylvie Garneau-Tsodikova, Micha Fridman and their colleagues from University of Michigan and Tel Aviv University have investigated the effect of 6′- and 6′′′-N-acylation of aminoglycosides on their ability to avoid bacterial resistance while retaining their antibiotic effect. The best compounds synthesised retained their full antibiotic effect against resistant strains whilst that of their parent compound was compromised. The authors have thus opened up a new route for aminoglycoside modification and demonstrated effective lead compounds for further development—the evolutionary struggle between man and pathogenic bacteria continues.

The referees enjoyed this paper and so did we, so read this HOT article in OBC today! It is free to access until 1st April 2011.

Assessment of 6′- and 6′′′-N-acylation of aminoglycosides as a strategy to overcome bacterial resistance
Pazit Shaul, Keith D. Green, Roi Rutenberg, Maria Kramer, Yifat Berkov-Zrihen, Elinor Breiner-Goldstein, Sylvie Garneau-Tsodikova and Micha Fridman
Org. Biomol. Chem., 2011, Advance Article

DOI: 10.1039/C0OB01133A, Paper

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HOT: Design of sophisticated supramolecular receptors

24 Feb 2011

Molecular self-assembly is an area of research that has spectacularly grown during the last two decades. The design of macromolecules that can adopt specific shapes and can act as receptors or host other molecules through non-covalent interactions has attracted particular attention.

One of the most popular building blocks in self assembly is calixarenes. However, although calix-[4]-arenes have been widely studied in the field of molecular recognition, calix-[6]-arenes have not received as much attention due to the flexibility of their skeleton. The design of calix-[6]-arenes is still a challenging task.

In this paper, Stephane Le Gac, Ivan Jabin and co-workers take advantage of the versatility of the calix[6]arene functionalization together with the flexibility of its skeleton to create additional host-guest and host-host interactions. The resulting supramolecular receptors are unique since these additional interactions are reminiscent of intra-protein interactions in biological receptors.

If you want to find out more about these unique supramolecular receptors, download this HOT paper which is free to access until 23rd March.

Allosterically driven self-assemblies of interlocked calix[6]arene receptors
Stéphane Le Gac, Jean-François Picron, Olivia Reinaud and Ivan Jabin
Org. Biomol. Chem., 2011
DOI: 10.1039/C0OB01020K

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HOT: New cationic lipo-thiophosphoramidates for gene delivery

24 Feb 2011

Paul-Alain Jaffrès et al. from the Université de Brest report the synthesis of cationic lipo-phosphoramidates and lipo-thiophosphoramidates possessing the capacity to compact and transfect plasmid DNA. They investigated the effect of different functional groups on the physico-chemical properties of the lipids and found that they could fine tune the fluidity and fusogenicity of the liposomes. The best of the thiophosphoramidates synthesised provided highly efficient transfection—even at low charge levels, in contrast to the older phosphoramidates—demonstrating that a minor modification of the chemical structure of the cationic lipids may have a direct impact on their gene transfection ability.

As all our HOT articles, this is free to access for 4 weeks (until 23rd March).

Cationic lipo-thiophosphoramidates for gene delivery: synthesis, physico-chemical characterization and gene transfection activity – comparison with lipo-phosphoramidates
Aurore Fraix, Tristan Montier, Nathalie Carmoy, Damien Loizeau, Laure Burel-Deschamps, Tony Le Gall, Philippe Giamarchi, Hélène Couthon-Gourvès, Jean-Pierre Haelters, Pierre Lehn and Paul-Alain Jaffrès
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB00981D

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HOT: DFT to predict outcome of microwave-assisted organic reactions

16 Feb 2011

Computational tools for predicting the viability of reactions are invaluable for making synthetic chemists’ lives easier, and this latest study makes another valuable addition to the metaphorical toolbox.

It is assumed that microwave irradiation assists organic reactions, such as Diels-Alder reactions, by rapid heating of the reactants. However, to date there are no computational studies which explain the role of microwaves on the course of these reactions.

Now, Maria Pilar Prieto and co-workers from the University of Castilla-La Mancha have used DFT to rationalise the activation of intramolecular Diels-Alder cycloaddition reactions under microwave conditions. They found that the activation energy of the reaction and the polarity of the stationary points on the reaction surface are good indicators of whether or not a reaction can be improved by microwave irradiation.

Read the full details of their findings online – the article is free to access for four weeks:

“In silico” mechanistic studies as predictive tools in microwave-assisted organic synthesis
A. M. Rodriguez, P. Prieto, A. de la Hoz and A. Díaz-Ortiz
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB01037E

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HOT: Biosynthetic pathway for 7-deazapurines

16 Feb 2011

Deazapurines are bicyclic heterocycles derived from purine where one nitrogen atom is replaced by a carbon. Although they have been widely studied in recent years, the mechanistic understanding of the biosynthesis of 7-deazapurines has always been intriguing.

There is a question that inevitably arise when looking at the biosynthetic pathway of deazapurines: Where does N-7 go?

Now, Professor Moody and his group at University of Nottingham have solved this mystery by using a doubly labelled purine-adenine and following it up by NMR spectroscopy and mass spectrometry.
Their conclusions are supported and support a recent study published in Biochemistry.

If you want to find out more about the fate of this nitrogen and the mechanistic understanding of the biosynthesis of deazapurines, read this HOT paper which is free to access until 16th March.

7-Deazapurine biosynthesis: NMR study of toyocamycin biosynthesis in Streptomyces rimosus using 2-13C-7-15N-adenine
Ugo Battaglia, Jed E. Long, Mark S. Searle and Christopher J. Moody
Org. Biomol. Chem., 2011
DOI: 10.1039/C0OB01054E

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HOT: Highly selective formation of lantibiotic conjugates

11 Feb 2011

Lantibiotics (and there is no spelling mistake) are a potential new class of antibiotics for clinical applications and food preservation. Their drawback is however their inability to penetrate the outer membranes of Gram-negative bacteria.

John Vederas and colleagues, at University of Alberta in Canada, try to overcome this problem by developing new ‘siderophores – transporters’ able to deliver lantibiotics to the targeted bacteria.

If you want to find out more about what happened next and the scope and limitation of siderophore-mediated drug transport for the development of new antibiotics download this HOT article which is free to access until 8th March.

Chemical synthesis and biological evaluation of gallidermin-siderophore conjugates
Sabesan Yoganathan, Clarissa S. Sit and John C. Vederas
Org. Biomol. Chem., 2011
DOI: 10.1039/C0OB00846J

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HOT: One step closer to the synthesis of an unstable antibiotic

10 Feb 2011

Nature has been giving organic chemists inferiority complexes for many, many years, so it is always good to see a neat piece of synthesis for a tricky natural product.

The structure of viridenomycin – an antibiotic with anti-tumor activity – has been known for 20 years, but attempts to synthesise it thus far have failed due to its complex structure and inherent instability. Now, Andy Whiting and colleagues from Durham University have synthesised fragments suitable for constructing a particularly unstable part of viridenomycin via a series of cross-coupling reactions.

They focused on the northern polyene fragment, synthesising several analogues with better isometric ratios and increased stability towards photoisomerisation than the original tetraene fragment. The authors hope that their method may help to achieve the total synthesis of this valuable complex molecule.

Read how they did it online – the article is free to access for 4 weeks!

Studies towards the synthesis of the northern polyene of viridenomycin and synthesis of Z-double bond analogues
Jonathan P. Knowles, Victoria E. O′Connor and Andrew Whiting
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB00977F

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HOT: Aryl azides go with the flow

10 Feb 2011

Organic azides are considered to be amongst the most hazardous chemicals and therefore not amongst the most popular within synthetic chemistry communities. In organic chemistry they are commonly used as a way to introduce an amine group, which makes them key compounds for synthetic chemists.

Steven Ley, Ian Baxendale and their group at University of Cambridge, describe in these back to back papers the development of a flow process for the synthesis of alkyl and aryl azides in high conversions. One of the key features of this flow procedure is the introduction of a new monolithic triphenylphosphine reagent that allows the use of triphenylphosphine in flow to provide high purity products without the need of further purification steps.

They also describe a general protocol for the in-line purification of the intermediates. They incorporate the azide synthesis and purification process into a multistep flow sequence to generate a collection of aminocyanotriazoles in a fully automated fashion.

Now you can read these very interesting and HOT papers which are free to access until the 8th March.

Download both papers here.

Flow synthesis of organic azides and the multistep synthesis of imines and amines using a new monolithic triphenylphosphine reagent
Catherine J. Smith, Christopher D. Smith, Nikzad Nikbin, Steven V. Ley and Ian R. Baxendale
Org. Biomol. Chem., 2011
DOI: 10.1039/C0OB00813C

A fully automated, multistep flow synthesis of 5-amino-4-cyano-1,2,3-triazoles
Catherine J. Smith, Nikzad Nikbin, Steven V. Ley, Heiko Lange and Ian R. Baxendale
Org. Biomol. Chem., 2011
DOI: 10.1039/C0OB00815J

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HOT: The workings of T. cruzi trans-sialidase

03 Feb 2011

T. cruzi, the causative agent of Chagas disease, relies on its enzyme trans-sialidase for part of its infectivity. Robert Field et al., from several collaborating institutions worldwide, have studied this enzyme, highlighting the wide range of structures and functionalities that it can accommodate. This study has demonstrated important features for potential inhibitor design (a therapeutic target for Chagas’ disease) and also opens up possibilities for using the versatility of this enzyme more generally as a catalyst for α-(2→3)-sialylglycoconjugate synthesis.

This HOT article is now free to access until 22nd February.

Probing the acceptor substrate binding site of Trypanosoma cruzi trans-sialidase with systematically modified substrates and glycoside libraries
Jennifer A. Harrison, K. P. Ravindranathan Kartha, Eric J. L. Fournier, Todd L. Lowary, Carles Malet, Ulf J. Nilsson, Ole Hindsgaul, Sergio Schenkman, James H. Naismith and Robert A. Field
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB00826E, Paper

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HOT: PBD-DNA adduct formation is reversible. Evidence by Thurston

02 Feb 2011

PBDs (pyrrolo[2,1-c][1,4]benzodiazepines) and their interaction with DNA is an area of active research.

PBDs belong to a family of biologically active an DNA-interactive antibiotics having unique mechanism of action compared with other DNA-binding agents. Up until now, there have been several reports in literature suggesting that PBD-DNA adduct formation might be reversible; however, no evidence of this reversibility had been reported.

For the first time, in this paper, David Thurston and colleagues at the School of Pharmacy at University of London, investigate the adduct formation of PBDs with DNA and its reversibility using HPLC/MS methodology and polarised light spectroscopy.

Read about some of their findings in this OBC HOT paper which is free to access until the 22nd February.

Observation of the reversibility of a covalent pyrrolobenzodiazepine (PBD) DNA adduct by HPLC/MS and CD spectroscopy
Khondaker M. Rahman, Colin H. James and David E. Thurston
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB00762E, Paper

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