Archive for the ‘Chemical Biology’ Category

A new system for cancer detection

While current cancer-diagnosis methods rely on an invasive biopsy or the detection of cancer-specific biomarkers, South Korean scientists have developed a simple and non-invasive detector for cancer cells that could speed up the early diagnosis of the condition, leading to a greater chance of survival for cancer patients.

Cancer cells fluorescing

Daunomycin interacting cancer cells viewed with fluorescene microscopy

Cancer cells have been found to differ from normal cells in several ways, including the make up of their cell membranes. Cancer-cell membranes have been found to contain more anionic lipids than normal cells, leading to an overall negatively charged cell surface. Yoon-Bo Shim and co-workers from Pusan National University, have exploited this negative surface charge to develop a probe based on daunomycin, an anti-cancer drug that is known to interact strongly with anionic lipids.

Read the full article in Chemistry World.

Read the original journal article:
Cancer cell detection based on the interaction between an anticancer drug and cell membrane components
Chem. Commun., 2013, 49, 1900-1902
DOI: 10.1039/C2CC38235K

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A new way to look at cancer cell detection

A novel cancer cell detection method, based on the interaction between daunomycin (DAN – an anticancer drug used in chemotherapy) and cell membrane components, has been developed by scientists in South Korea.

The method uses the electrochemical and fluorescence behaviour of DAN and uses an aptamer probe immobilised on a conducting polymer-gold nanoparticle composite film.

he aptamer sensor probes using electrochemical impedance spectroscopy and fluorescence microscopy. The method differentiates between cancerous and non-cancerous cells at low concentrations (0.01μM).

Read the ‘HOT’ Communication in full:

Cancer cell detection based on the interaction between an anticancer drug and cell membrane components
Pranjal Chandra , Hui-Bog Noh and Yoon-Bo Shim
Chem. Commun., 2013, DOI: 10.1039/C2CC38235K

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Early Alzheimer’s diagnosis compound

Alzheimer’s disease is the most common form of dementia and, as there is no cure, early diagnosis is crucial for treatment to be effective. To this end, UK and US scientists have developed a labelled tracer compound that binds to plaques closely associated with Alzheimer’s disease (AD) so that the plaques can be picked up by a medical imaging technique.

The tracer compound is a [18F]-labelled barbiturate and is used with the imaging technique positron emission tomography (PET). Although other radiolabelled compounds have been used as PET tracers, using [18F]-labelled barbiturates for molecular imaging in AD has distinct advantages, such as good blood-brain barrier crossing ability, metabolic stability and easy accessibility.

Tree that looks like a face with some leaves blowing away to represent memory loss in Alzheimer's diseaseAs Alzheimer’s disease advances, symptoms can include confusion, irritability and aggression, and long-term memory loss © Shutterstock

 Matteo Zanda at the University of Aberdeen and colleagues, in conjunction with Pfizer in the US, developed several fluorinated barbiturate analogues. The key to developing an effective molecular imaging radiotracer is the ability to distinguish between a healthy individual and someone suffering from a neurological disease, such as AD, they say. Barbiturates have a strong capacity for forming structures with biopolymers and are effective metal ion chelators. As such, the team thought that they would bind to AD-related plaques, which consist of the biopolymer β-amyloid and metal cations, such as Zn(II) and Cu(II).

See the Chemistry World story in full or read the Chem Comm article:

18 F-barbiturates are PET tracers with diagnostic potential in Alzheimer’s disease
Elisa Calamai , Sergio Dall’Angelo , David Koss , Juozas Domarkas , Timothy J. McCarthy , Marco Mingarelli , Gernot Riedel , Lutz F. Schweiger , Andy Welch , Bettina Platt and Matteo Zanda
Chem. Commun., 2013,49, 792-794
DOI: 10.1039/C2CC38443D

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Spinks Symposium 2013: Regenerative Medicine – registration open

 28 January 2013 

Chemistry Centre, Burlington House, London

The therapeutic promise of regenerative medicine, as a way to restore aging or damaged tissues and organs, is one of the most exciting areas of medicines research. With the proportion of older people increasing, degenerative and chronic diseases are a major challenge. To move forward, the chemical sciences have a vital role to play in understanding

  • disease mechanisms
  • signalling of stem cells
  • cellular differentiation
  • new methodologies for surface modification

The 2013 Spinks Symposium will explore the critical issues that underpin developments in regenerative medicine and provide a clear understanding of the challenges involved in translating research outputs into application. Particular emphasis will be put on how medicinal chemistry/chemical biology research might provide a springboard to therapeutic development. Researchers from industry, academia and the wider health sciences sectors will join together for this stimulating workshop, including oral presentations discussion groups, flash presentations and a comprehensive poster session.

How can I get involved?

  • Abstracts for the poster programme are now invited. Take full advantage of this exceptional opportunity to present your work and submit before Friday 21st December.
  • Registration is also open and if you would like to benefit from the early bird rates be sure to secure your place before Friday 21st December
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Drug delivery: implications of gold-protein interactions

Researchers in Italy have shown that medicinal gold compounds interact strongly with the proteins of the copper trafficking system, which could have implications for drug delivery.

The copper trafficking system consists of proteins that help the uptake of copper into cells and then promote its transfer and delivery to copper-dependent cellular proteins.  One of these ‘chaperones’ is known as Atox-1.

Copper trafficking within a mammalian cell

Previous work has shown that platinum-based anticancer drugs strongly interact with copper trafficking system proteins and Messori and co-workers hypothesised that medicinal gold compounds might also do the same, especially in the +1 oxidation state; soft lewis acids, such as gold (I) ions react eagerly with Atox-1.

The interactions of three gold (III) compounds with Atox-1 were analysed through ESI-MS and revealed the formation of metal-protein adducts. The same major adduct was invariantly formed, matching the protein binding of a single gold (I) ion. Formation of this adduct implied that the gold (III) complex had broken down, a loss of ligands and reduction to a gold (I) species. ESI-MS also displayed peaks that corresponded to protein binding with two gold (I) ions. A stability study showed that one of the three gold-protein adducts was stable over 72 hours.

From their findings, the authors conclude that the cytotoxic gold compounds investigated form stable adducts with copper chaperone, Atox-1. These results have implications for medicinal drug design and our little friend, Atox-1 stays in a job.

Read this HOT Chem Comm article today (free to access until the 14th of December 2012):

Medicinal gold compounds form tight adducts with the copper chaperone Atox-1: biological and pharmacological implications
Chiara Gabbiani, Federica Scaletti, Lara Massai, Elena Michelucci, Maria A. Cinellu and Luigi Messori
Chem. Commun., 2012, 48, 11623-11625

Published on behalf of Sarah Brown, Chemical Communications web science writer.

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Origami, without the papercut, visualised

Researchers in China have been able to visualize the intracellular location of DNA origami with a label-free fluorescent probe.

But let’s unfold a few things first and figure out what that means. DNA origami is the folding of a strand of DNA to make arbitrary 2 or 3 dimensional shapes; this serves as a ‘scaffold’ for shorter DNA strands that help hold the structure in its folded shape. These structures may be used for drug delivery, biosensors and more. I once made an origami frog; I wonder if there are any similarities…

Direct visualisation of the distribution and stability of DNA origami in live, cellular systems has not been achieved. Fluorescent labels can be attached to DNA strands but these have their drawbacks, such as weak emission intensity, photobleaching and expensive. Ding and co-workers looked at alternatives to visualize DNA origami in live cells.

The group were inspired by research on a series of carbazole-based cyanine fluorescence probes, which have a weak emission when they are monomolecularly dissolved but switch to a strong luminescent state upon binding to DNA or protein molecules.  The significant enhancement is attributed to restricted intramolecular rotational (RIR) motions by anchoring the DNA molecules, which causes the large reduction in the non-radiative decay of fluorescence molecules.

DNA-origami visualised in cells

Follow the instructions (a) and you too won’t make DNA-origami visualised in cells (b)

Ding and co-workers then took some tubular DNA origami, the cyanine fluorophore and found that the carbazole-based cyanine molecules could be used as a sensitive optical switch, turned on when DNA origami is detected and turned off when the nanostructure degrades. After incorporating the cyanine probe molecules, the DNA origami-probe complex was administered to live cells. Excitingly, the green-yellow frog… erm, I mean, fluorescence was visible inside the cells treated with the probe. The group went further to try and understand the internalization mechanism of the DNA origami and found the probe localized in lysosomes. Finally, degradation studies showed that most DNA origami were dissociated after 60 hours, also a bit like my origami frog.

Unlike my attempts at origami, Ding and co-workers have demonstrated an exciting step in scaffolded DNA origami and its future applications in nanomedicine.

Read this HOT Chem Comm article today (free to access until the  5th of December 2012):

Visualization of the intracellular location and stability of DNA origami with a label-free fluorescent probe
Xibo Shen, Qiao Jiang, Jinye Wang, Luru Dai, Guozhang Zou, Zhen-Gang Wang, Wei-Qiang Chen, Wei Jiang and Baoquan Ding
Chem. Commun., 2012, 48, 11301-11303

Published on behalf of Sarah Brown, Chemical Communications web science writer.

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ChemComm celebrates its first Gold for Gold communication

Eugen Stulz (University of Southampton) and colleagues are the first ChemComm authors to publish a communication as part of our Gold for Gold initiative.Gold Image

Their communication, entitled ‘A DNA based five-state switch with programmed reversibility’ is now free to access for all.

‘I’m delighted that Eugen’s communication is the first open access communication to be published in ChemComm using the RSC’s Gold for Gold programme,’  says Phil Gale, Head of Chemistry at the University of Southampton. ‘This open access programme will allow us to showcase our research to a much wider audience.’

Gold for Gold is an innovative initiative rewarding UK RSC Gold customers with credits to publish a select number of papers in RSC journals via Open Science, the RSC’s Gold Open Access option.

More information on Gold for Gold is available on our website. If you have any questions on the procedure, or are an interested customer from outside the UK, please contact goldforgold@rsc.org.

Also of interest:
Gold for Gold – First Open Access credit used by University of Hull

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Biocatalysis: an article collection

Beers, wines and cheeses are enjoyed around the world today and have been for millennia. In fact the practices of brewing and cheese-making pre-date recorded history so it is difficult to accurately determine when we first started using naturally occurring enzymes and microorganisms to create valuable (and in this case, tastier!) products.

Biocatalysts are of course used in far more diverse applications than the creation of food-stuffs, including in many organic syntheses and in the generation of fine chemicals. Due to their natural design, they can offer superior selectivity for particular products and have a far lower environmental impact than many traditional catalysts. Our knowledge and understanding of biocatalysts has increased dramatically in the last few decades, which has allowed us to develop biologically modified and biomimetic catalysts for a range of applications. 

To keep you up to date with the latest advances in this rapidly expanding field we have collected together these high impact articles and made them free to access until the 31st October!

Click here for the full list of free articles

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ChemComm and the chemistry-biology interface

The chemical sciences make a huge contribution to solving challenges in the biological sciences. 

So quite rightly, articles at the chemistry–biology interface make up an important part of ChemComm.   

Here’s a selection of some recent articles, all free to access until 19th October

Nucleic acid aptamers: an emerging frontier in cancer therapy
Guizhi Zhu, Mao Ye, Michael J. Donovan, Erqun Song, Zilong Zhao and Weihong Tan
Chem. Commun., 2012, DOI: 10.1039/C2CC35042D 

Picomolar level profiling of the methylation status of p53 tumor suppressor gene by label-free electrochemical biosensor
Po Wang, Hai Wu, Zong Dai and Xiaoyong Zou
Chem. Commun., 2012, DOI: 10.1039/C2CC35615E 

Oriented Immobilization of Oxyamine-Modified Proteins
Long Yi, Yong-Xiang Chen, Po-Chiao Lin, Hendrik Schroeder, Christof M. Niemeyer, Yaowen Wu, Roger S. Goody, Gemma Triola and Herbert Waldmann
Chem. Commun., 2012, DOI: 10.1039/C2CC35237K 

Colorimetric detection of single-nucleotide polymorphisms with a real-time PCR-like sensitivity
Wei Shen, Huimin Deng, Alan Kay Liang Teo and Zhiqiang Gao
Chem. Commun., 2012, DOI: 10.1039/C2CC35070J

A bioresponsive controlled-release biosensor using Au nanocages capped with an aptamer-based molecular gate and its application in living cells
Wei Wang, Tao Yan, Shibin Cui and Jun Wan
Chem. Commun., 2012, DOI: 10.1039/C2CC33165A

Cascade imaging of proteolytic pathway in cancer cell using fluorescent protein-conjugated gold nanoquenchers
Kyoungsook Park, Jinyoung Jeong and Bong Hyun Chung
Chem. Commun., 2012, DOI: 10.1039/C2CC35687B

Eager for more? 

Check out the Nucleic acids: new life, new materials web theme, jointly organised with OBC and RSC Advances.

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Glucometers altered to detect HIV

Glucometers used by diabetic patients can be altered to detect HIV-related DNA sequences, say scientists in China.

The commercially available personal glucometer has been the most successful point-of-care (POC) device up to date. But the glucometer only responds to glucose. Extending its use to monitoring different types of targets would potentially revolutionise POC technology.

The team used invertase, an enzyme that catalyses the hydrolysis of sucrose into glucose, to interpret DNA recognition events into readouts measurable by the glucometer.

They loaded nanoparticle amplification labels with invertase, which, through target/probe DNA hybridisations, catalysed the conversion of sucrose on the sensing surface to glucose. They could detect as low as 0.5pM of target DNA. While they demonstrate the method with HIV DNA, it could potentially used to detect different DNAs.

Graphical Abstract

 

Link to journal article
Sensitive point-of-care monitoring of HIV related DNA sequences with a personal glucometer
J Xu et al
Chem. Commun., 2012, DOI: 10.1039/c2cc35941c

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