The importance of chemistry in sequencing nucleic acids

 

Solid phase DNA sequencing

Chemistry has played a vital role towards making routine, affordable sequencing of human genomes a reality. Leading UK scientist, Shankar Balasubramanian, provides a compelling review of the last 60 years, from the Sanger sequencing method through to the human genome project. In particular, Balasubramanian focuses on the achievements of Solexa (latterly, Illumina) on the modern developments of high throughput nucleic acid sequencing that originated in Cambridge, in the UK.
   

In association with the International Year of Chemistry (IYC), this Highlight in Chemistry emphasises the importance of chemistry and how it continues to contribute towards many other fields, most notably the biological and biomedical sciences. This sequencing approach is helping to transform science and offers intriguing prospects for the future of medicine.

Fancy reading more? Download the ChemComm Highlight, which will be free to access until the 1st July 2011.

 For your info, ChemComm is publishing Highlights in Chemistry articles throughout 2011, which has been recognised as an official activity for celebrating the IYC. Take a look at the IYC website to keep up-to-date on what else is happening throughout 2011 to celebrate the achievements of chemistry and its contributions to the well-being of humankind.

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Totally synthetic over bryostatin

UK scientists demonstrate the total synthesis of 20-deoxybryostatin for the first time

Bryostatins are macrocyclic natural products with various biological activities, including potent anti-cancer activity due to protein kinase C inhibition. Eric Thomas and his team from the University of Manchester have shown that it is possible to prepare 20-deoxybryostatin, using a modified Julia olefination to form the tricky 16,17-double-bond, followed by macrolactonisation, selective deprotection and oxidation.Fancy finding out more about the reaction conditions?

Download the ChemComm communication, which will be free to access until the 1st July 2011. 

20-deoxybryostatin

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Cram Lehn Pedersen Prize – now open for nominations

Recognising significant original and independent work in supramolecular chemistry

 

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Imaging brain tumours

A new probe for imaging brain tumours could offer increased hope for cancer patients, say Chinese chemists.

Den-Angio visualizes an orthotopic U87MG tumor non-invasively in vivo. (A) NIR fluorescence and X-ray/color coded NIR fluorescence images of a mouse head at 2 h PI of Den-Angio. Arrows point to the tumor. (B) T1-weighted MR images of a mouse brain (coronal plane) at 2 h PI of Den-Angio or Gd3+–DTPA with the same gadolinium dose (0.05 mmol kg−1). White arrows point to the tumor and red arrows point to the cerebral ventricle. (C) Histological H&E staining of identical brains in panel B. Scale bar, 2 mm.Cong Li, at Fudan University, Shanghai, and colleagues have made a dendrimer-based nanoprobe called Den-Angio that can cross the blood-brain barrier. It can be used in the magnetic resonance imaging of brain tumours and should make it easier for doctors to distinguish cancerous tissue from healthy cells when cutting out the tumour.

To find out more, read Li’s ChemComm communication.

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Inducing protein heterodimerisation

Scientists in The Netherlands and Germany have shown that cucurbit[8]uril (CB[8]) induces selective heterodimerisation between two different proteins.
 

Supramolecular induced protein dimerisation

Luc Brunsveld and his team functionalised the two proteins with methylviologen (electron deficient) and napthalene (electron rich) guest molecules, which formed a charge transfer complex inside the CB[8] cavity.  Interestingly, the resulting dimerisation can be visually observed and has established that there is distinct interplay between the supramolecular components within the proteins.

Fancy reading more? Then download the ChemComm communication,which will be free to access until the 24th June 2011.

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Ibuprofen: anticancer drug

Scientists in the UK have moved a step closer to understanding how ibuprofen could help treat cancer. The findings could lead to the drug being used as a preventative treatment for prostate cancer, in the future.

Ibuprofen – a common painkiller – can help reduce the risk of prostate cancer, but the mechanism by which it inhibits tumour cells is still not fully understood. Now, Matthew Lloyd and his team from the University of Bath in the UK, in collaboration with Cancer Research UK, have uncovered a mechanism suggesting that the chiral inversion of ibuprofen inhibits the activity of the protein alpha-methylacyl-CoA racemase (AMACR), levels of which are increased in the presence of prostate, some colon and other cancers.

To find out more, read the full news story in Chemistry World and download Lloyd’s ChemComm communication.

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Regenerating electrochemical immunosensor

A highly sensitive and regenerative electrochemical immunosenor has been created by scientists in China, by combining a 3D tetrahedra-structured probe (TSP) and a DNA-bridged antibody immobilisation technique.

Immunological TSP sensor

Chunhai Fan and colleagues from the Shanghai Institute of Applied Physics collaborated with scientists from the Nanjing University of Science and Technology. Together the team alleviated common problems associated with electrochemical biosensors, such as poor reproducibility and orientation of surface confined molecules, by using the TSP. Next, the team assembled the TSP onto the gold surface with high reproducibility, resulting in controlled spacing and orientation of the DNA probes. Antibodies were then reversibly anchored to the nanostructured surface via a DNA bridge, producing the immunological (iTSP) platform.

Fan believes that the iTSP platform will be a promising tool for various immunological assays, as well as DNA-programmed protein microarrays for future proteomic studies, and here’s a summary of the reasons why:-

  1. This paper shows a simple one-step process to create the iTSP, which leads to a stable and reproducible surface for the anchoring of antibodies.
  2. Conjugated antibodies are separated from the surface by a relatively thick iTSP layer, preventing possible surface-induced effects.
  3. The protein resistant ability of iTSP is crucial for the proper orientation of the antibody conjugates and minimizes nonspecific adsorption that is often found in immunosensors.
  4. The hollow structure of the tetrahedra makes it possible for redox molecules to easily penetrate the thick layer, supporting sensitive electrochemical detection.
  5. The iTSP platform supports regeneration of the surface by using mismatched complementary DNA, which forms the basis of reusable immunosensors.

Fancy reading more? Then download the ChemComm communication, which will be free to access until the 24th June 2011.

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Final stop for the ChemComm Symposium

The international speakers assembled early on Thursday morning to make the final journey to Nankai University, Tianjin. After a flight and a two hour journey on the ChemComm minibus, we arrived at our hotel directly opposite the entrance gates to Nankai University. The first thing that struck us about the hotel was the enormous rooms. I actually got lost in mine between the two bathrooms, the study and the lounge area. Apparently they were all like this – what a hotel!

After a formal dinner with our host Professor Qilin Zhou (Director of the State Key Laboratory of Elemento-organic Chemistry and member of the Chinese Academy of Sciences), most retired to bed but Professor Rawal, Professor Maruoka and I were taken to a live Chinese comedy show. Lots of clapping with plastic clapping hands, much laughter and, of course, all sketches in Chinese. It was a great experience even if we did not understand anything apart from ‘hello’ and ‘thank you’.

The following day started with eager anticipation as an audience in excess of 100 watched Professor Feringa give his final scientific presentation on motors and switches. He was followed by local Professor of Energy, Yun Chen, who spoke about some of his latest research into new nanomaterials for batteries, a key challenge with the ever increasing energy demands around the world. Before lunch, Veronique Gouverneur gave her presentation looking at the latest developments in organofluorine chemistry.

After lunch, the five poster judges took to their duties for one last time with each asked to examine ten posters and select just one. With the final five selected it was left to Professors Feringa and Maruoka to rank the winners. All five received money from the State Key Lab thanks to the generosity of Professor Zhou, plus journal subscriptions and books from the RSC, amongst other things, as additional gifts.

The scope of the meeting then switched to green chemistry as Professor Buxing Han spoke about his latest research using ionic liquids, supercritical fluids and a mixture of the two as solvents for organic reactions. Professor Han was followed by Professor Rawal who gave his third different talk in five days covering his group’s total synthesis of a member of the Welwitindolinone group of natural products. This was a particularly insightful talk as Professor Rawal not only discussed things that worked but also routes that had failed. There was certainly a good lesson here for total synthesis students, namely things may not always work out but perseverance is the key to success.

In the last session of the day, Professor Maruoka spoke about some of his latest results in the field of organocatalysis. He was followed by Zhen Yang who gave a second total synthesis masterclass. The retrosynthetic analysis slides certainly gave me a trip down memory lane and the overall synthesis in 26 steps (micrandilactone) showcased the real power of organic chemistry and the creative thought processes needed to succeed.

After the poster presentations had been made, the speakers and other key faculty members walked to a very famous restaurant called Goubuli for steamed dumplings. They are a local speciality, filled with vegetables, fish and, traditionally, pork. Normally six is enough, but I was proud to exceed the average! The other highlight of the dinner was the stinky tofu, a delicacy providing you can get past the tremendously bad smell, much stronger than the bluest blue cheese. This was a real challenge – the stink was just so bad!

After dinner, the speakers and faculty members retired to a German bar for one last drink to celebrate the day and the past week. Over the course of the seven days we had travelled many thousand of miles, seen 21 scientific talks covering many different aspects of the chemical sciences, with a total audience close to 700 and nearly 200 posters judged. All in all, it was a great week and the only thing left to do is to thank all the speakers and, of course, the local hosts, without whom none of this would have been possible.

Robert Eagling

View the Nankai Symposium schedule

Related posts:

ChemComm Symposium heads west…..

The 5th ChemComm International Symposium gets underway….

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A refreshing limonoid synthesis

The challenging synthesis of B-seco limonoids has been achieved using an Ireland-Claisen rearrangement, report scientists in Germany.

Herbert Waldmann worked with a collaboration of scientists from various German science institutes on this project and believes that the synthetic strategy described here might facilitate the total synthesis of other natural products containing similar limonoid scaffolds and their analogues.

For more details on the reaction conditions used, download the ChemComm communication today, which will be free to access until the 24th June 2011.

You may also be interested to know that Herbert Waldmann recently helped guest edit a web themed issue on ‘Enzymes and Proteins’ – A nice collection of articles from high profile scientists in this area of chemical biology, including some of Herbert’s very own research papers.
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Macrocycles for in vivo zinc sensing

Graphical abstract: Modular ‘click’ sensors for zinc and their application in vivoZinc anions are ubiquitously present in the body and involved in many metabolic pathways affecting the proper functioning of the immune system, DNA transcription, reproduction, sexual development, brain function, and more roles are uncovered by studies worldwide.

The presence of abnormally high or low level of zinc in specific organs and areas has been linked to several diseases and conditions, including Alzheimer’s disease, stroke and epilepsy. In the light of these considerations, it is not surprising that many efforts have been devoted to in vivo zinc sensing and quantification.

A significant portion of the research to uncover the correlations between the concentration of metal ions, pathologies and development is performed on animal models such as zebrafish (Danio rerio). Due to their fast development, they can be grown outside the mother’s body, and their embryos are transparent, allowing for a clear observation of their organs without the need for dissection.

Watkinson and Goldup, from Queen Mary University of London, recently focused their effort to the development of a fluorescent sensor for zinc to be used in model studies on zebrafish. The sensor is based on macrocyclic nitrogen-containing rings (cyclen or cyclam) equipped with a fluorescent pendant arm, introduced using a widely known and applied “click” cycloaddition. The sensor’s fluorescence is activated upon coordination of the zinc anion in a scorpionate fashion.

The sensors proved reliable and stable in a wide range of pH, ideal for in vivo use, and a remarkable selectivity for zinc over other possible anions. Competition experiments with twelve different anions showed that only in the presence of Fe3+ and Cu2+ in threefold excess (in relation to zinc) the sensor failed to discriminate between the metals.

To test their performance in biological models, zebrafish eggs were grown in solutions of the sensors and the distribution of fluorescence monitored during their growth, proving not toxic to the subjects. The accumulation of fluorescence concentrated in the eye, the gall bladder and the biliary system, all regions not highlighted by previous sensors, suggesting a different mechanism of absorption for these macrocyclic compounds and different cell permeability.

Although those reported are preliminary results, the characteristics of these sensors may make them a viable candidate for future applications in vivo sensing of zinc pools.

Read the article online or access the ESI (free).

Modular ‘click’ sensors for zinc and their application in vivo
Kajally Jobe, Caroline H. Brennan, Majid Motevalli, Stephen M. Goldup and Michael Watkinson
Chem. Commun., 2011, 47, 6036-6038

Posted on behalf of Dr. Giorgio De Faveri, Web Writer for Catalysis Science & Technology 

This communication is part of the ChemComm Supramolecular Chemistry web themed issue. Check out the web theme page to download other contributions from this exciting issue.

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