HOT: multivalent strategies for RGD peptide-integrin binding

Integrins play important roles in cell adhesion and signalling, and crucially are over-expressed in certain cancer cells.  The tripeptide Arg-Gly-Asp (RGD) is known to bind to integrins, and understanding exactly how they bind is obviously of fundamental importance for the development of structures with higher integrin affinities for possible therapeutic applications.

Here, Daniel Welsh and David K. Smith (University of York) investigate different ways in which the peptide ligands can be organised for multivalent binding to integrins. Although integrins only posses a single binding site they often grouped together in cell membranes, so mutlivalent binding to multiple integrins is possible.  They investigate both dendritic (covalent) and self-assembly (non-covalent) strategies, finding both can be used in similar ways to enhance the binding of RGD peptides to integrins, but that the self-assembly approach appears to give rise to slightly higher affinity integrin binding.

To find out more download this article – it’s free for the next four weeks:

Comparing dendritic and self-assembly strategies to multivalency—RGD peptide–integrin interactions
Daniel J. Welsh and David K. Smith
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C1OB05241A

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HOT: sweet but not sickly – non-cytotoxic sugar amino acid-containing antimicrobial agents

As bacteria continue to resist our efforts to eradicate them, the development of new antibiotics with alternative modes of action are required to augment existing treatments.  Cationic antimicrobial peptides (CAPs) show potential, but are often too cytotoxic to be developed as new antibiotics.  One way to get around the cytotoxic mechanisms is to attach agents to carriers, such as gold nanoparticles which are non-toxic to cells and biocompatible.

In this HOT paper Tushar Kanti Chakraborty and colleagues from the Central Drug Research Institute, India, have synthesised some novel sugar amino acid-containing cyclic cationic peptides and attach them to gold nanoparticles to study their therapeutic effects. The preliminary studies found that the sugar amino acid-containing CAPs retained their antimicrobial activity on conjugation with the nanoparticles, but with significantly reduced cytotoxic effects.

Download the article to discover more about the study and the potential mechanism for these CAPs – it’s free to access for four weeks:

Towards the synthesis of sugar amino acid containing antimicrobial noncytotoxic CAP conjugates with gold nanoparticles and a mechanistic study of cell disruption
Sudip Pal, Kalyan Mitra, Sarfuddin Azmi, Jimut Kanti Ghosh and Tushar Kanti Chakraborty
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C1OB05338H

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Free Radical Chemistry themed issue in memory of Athel Beckwith

Professor Athel Beckwith who inspired a generation of free radical chemists

View the Free Radical Chemistry web themed issue

It was a stunned international chemistry community that learnt of the tragic death of Athel Beckwith on 15 May 2010. As word spread, shock and disbelief were the overwhelming sentiments; the world had lost a scientific treasure.

Athel Beckwith was born in Perth on 20 February 1930. His father was a pharmacist and both of his parents were gifted musicians, a trait passed on to Athel at an early age. He attended Perth Modern School where he excelled. He matriculated with Distinction in all seven subjects and went on to the University of Western Australia for his chemical education. It was during his undergraduate studies that Athel learnt that the most interesting chemistry occurs when there is an unexpected outcome and that it is through these unexpected outcomes that we learn new things. These are principles that he passed on to his students during his academic career including myself.

Athel spent his Honours year working on natural product chemistry under the guidance of Doug White, and later on reaction mechanisms with Joe Miller. After a period as a graduate assistant he moved to Adelaide to take up a position as a junior lecturer, but eventually doctoral studies lured Athel to Oxford where he worked with Professor Waters on relatively unknown entities known as “free radicals”, a “wise choice” according to Athel.

After a year at Imperial College on a Nuffield Foundation grant he returned to Adelaide where he established a research group working on free radicals and shortly after became Professor of Organic Chemistry at the age of 35. This was a very important period in the development of free radical chemistry and led to “Beckwith’s Rules” for predicting the outcomes of free radical cyclization reactions. In 1981 he moved to the Australian National University where he remained until his retirement in 1995.

I know of only three reactions that are named after Australian chemists (Birch, Liepa and Beckwith–Dowd) and, it is significant that they all involve free radicals. It was carrying out a Birch reduction as an undergraduate that swayed me toward chemistry and eventually free radicals and I was fortunate to work under Athel’s guidance during my PhD studies. Athel was at the cutting edge of free radical chemistry during what I have referred to as the “Free Radical Renaissance Period” and others have called the “Golden Age” during which the factors that govern radical chemistry were being teased out to provide guidelines that we now all take for granted. His contributions to the understanding of factors that govern the region- and stereo-selectivity of radical reactions are profound and enduring and established Australia as a major hub of activity in the field, a hub that several of his “academic children” have inherited. He also made significant contributions to radical clock reactions, nitroxide chemistry, the neophyl and other rearrangements, ESR spectroscopy, as well as other chemistries.

I have tried to model my role as supervisor to his “scientific grandchildren” on the principles that he taught me; even if I perform my role to only a fraction of Athel’s ability, I would consider that to be a great achievement. In addition to being a brilliant scientist, Athel was always kind, a gentleman and a scholar in the truest sense, a wonderful human being.  Further information about Athel can be found in a recent interview for the Australian Academy of Science (http://www.science.org.au/scientists/interviews/b/ab.html).

It has been a pleasure to be the guest editor of this special free radical themed issue of Organic & Biomolecular Chemistry dedicated to Athel. It is timely that the latest free radical chemistry be showcased in such a manner, and I am confident that Athel would have appreciated reading each of the cutting-edge articles presented in this special issue. Fittingly, a diversity of radical chemistry from around the world is represented in this issue, of which about 25% of articles have been flagged as being HOT. The overwhelmingly positive responses from members of the international free radical community to invitations to contribute to this issue is a measure of the fondness and esteem that Athel Beckwith was held in and I thank each of you for making this issue such a success.  I also thank the Team at Organic & Biomolecular Chemistry, in particular Lorena Tomas Laudo, Roxane Owen and Richard Kelly for their professional expert assistance, guidance and good humour.

Carl Schiesser – Guest Editor

 

Carl Schiesser is Professor of Chemistry in the School of Chemistry at The University of Melbourne and Director of the Australian Research Council Centre of Excellence for Free Radical Chemistry and Bio­technology. He received his PhD in 1987 from the Australian National University working with Professor Athel Beckwith and was a postdoc with Professor Alwyn Davies at University College London from 1988–1990. Professor Schiesser received a DSc from the University of Adelaide in 2000 and was awarded the prestigious A. J. Birch medal of the Royal Australian Chemical Institute in 2006.  Carl is a Fellow of the Royal Australian Chemical Institute and the Royal Society of Chemistry. He has extensive experience in free radical chemistry, ranging from molecular modelling, through to mechanistic and kinetic studies, the development of new chemical methodology, synthesis of bioactive molecules and cultural materials conservation.

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Top ten most accessed articles in April

This month sees the following articles in OBC that are in the top ten most accessed:-

Carbohydrate chemistry in drug discovery 
M. Carmen Galan, David Benito-Alifonso and Gregory M. Watt 
Org. Biomol. Chem., 2011, 9, 3598-3610 DOI: 10.1039/C0OB01017K  

Gold-catalysed synthesis of amino acid-derived 2,5-disubstituted oxazoles 
Christopher L. Paradise, Pooja R. Sarkar, Mina Razzak and Jef K. De Brabander 
Org. Biomol. Chem., 2011, 9, 4017-4020 DOI: 10.1039/C1OB05390F 

Mannich-Michael versus formal aza-Diels-Alder approaches to piperidine derivatives 
P. Ricardo Girling, Takao Kiyoi and Andrew Whiting 
Org. Biomol. Chem., 2011, 9, 3105-3121 DOI: 10.1039/C0OB00996B, Perspective 

The stimulating adventure of KRN 7000 
Aline Banchet-Cadeddu, Eric Hénon, Manuel Dauchez, Jean-Hugues Renault, Fanny Monneaux and Arnaud Haudrechy 
Org. Biomol. Chem., 2011, 9, 3080-3104 DOI: 10.1039/C0OB00975J  

Highly selective fluorescent OFF-ON thiol probes based on dyads of BODIPY and potent intramolecular electron sink 2,4-dinitrobenzenesulfonyl subunits 
Huimin Guo, Yingying Jing, Xiaolin Yuan, Shaomin Ji, Jianzhang Zhao, Xiaohuan Li and Yanyan Kan 
Org. Biomol. Chem., 2011, 9, 3844-3853 DOI: 10.1039/C0OB00910E 

Mild preparation of functionalized [2.2]paracyclophanes via the Pummerer rearrangement 
Matteo Montanari, Alberto Bugana, Arvind K. Sharma and Dario Pasini 
Org. Biomol. Chem., 2011, Advance Article DOI: 10.1039/C1OB05319A  

Rhodamine-based highly sensitive colorimetric off-on fluorescent chemosensor for Hg2+ in aqueous solution and for live cell imaging 
Hengguo Wang, Yapeng Li, Shufei Xu, Yanchun Li, Chen Zhou, Xiaoliang Fei, Lei Sun, Chaoqun Zhang, Yaoxian Li, Qingbiao Yang and Xiaoyi Xu 
Org. Biomol. Chem., 2011, 9, 2850-2855 DOI: 10.1039/C0OB01032D, Paper 

Energy transfer cassettes in silica nanoparticles target intracellular organelles 
Jiney Jose, Aurore Loudet, Yuichiro Ueno, Liangxing Wu, Hsiang-Yun Chen, Dong Hee Son, Rola Barhoumi, Robert Burghardt and Kevin Burgess 
Org. Biomol. Chem., 2011, 9, 3871-3877 DOI: 10.1039/C0OB00967A  

A ratiometric near-infrared pH-responsive fluorescent dye based on distyryl BODIPY 
Hui He and Dennis K. P. Ng 
Org. Biomol. Chem., 2011, 9, 2610-2613 DOI: 10.1039/C0OB01252A, Communication 

A specific chemodosimeter for fluoride ion based on a pyrene derivative with trimethylsilylethynyl groups 
Hua Lu, Qiuhong Wang, Zhifang Li, Guoqiao Lai, Jianxiong Jiang and Zhen Shen 
Org. Biomol. Chem., 2011, Advance Article DOI: 10.1039/C1OB05164D  

Why not take a look at the articles today and blog your thoughts and comments below.

Fancy submitting an article to OBC? Then why not submit to us today or alternatively email us your suggestions.
   

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OBC themed issue on foldamer chemistry – Call for papers

OBC is delighted to announce a high-profile web theme focussing on foldamer chemistry. Submissions are now open.

This online theme issue will be published at the end of 2011. Submissions of communications and full papers can be made at any time but must be received by the editorial office by 15 August 2011 for peer review.

Submission and tracking of manuscripts can be done directly online at http://mc.manuscriptcentral.com/ob. Submissions should indicate in the “comments to the editor” section that they are for the foldamers web theme.

You can view other, recently published OBC web themes at http://pubs.rsc.org/en/journals/journalissues/ob#!themedissues

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OBC Issue 11 published!

Check out the cover articles in Organic & Biomolecular Chemistry Issue 11.

The outside cover features work by Michael Doyle and colleagues  at University of Maryland. They talk about catalytic C-H insertion processes in comparison with other approaches for the synthesis of selected synthetic targets, lactones and lactams, which have been of biological or medicinal interest. It is a very interesting and original review article. Read more at

Intramolecular catalytic asymmetric carbon–hydrogen insertion reactions. Synthetic advantages in total synthesis in comparison with alternative approaches
Michael P. Doyle, Maxim Ratnikov and Yu Liu
Org. Biomol. Chem., 2011, 9, 4007-4016
DOI: 10.1039/C0OB00698J

The inside cover represents how Aminoglycoside acetyltransferase AAC(6’) belonging to the aminoglycoside-modifying enzymes (AMEs) does not deactivate the 6’-N-glycinyl tobramycin which attacks the bacterial ribosome (green arrow). In contrast, the parent aminoglycoside tobramycin cannot pass through bacterial resistance mechanism (red arrow).
You can read more about this article by Micha Fridman, Sylvie Garneau-Tsodikova and co-workers at Michigan and Tel Aviv at

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, 9, 4057-4063
DOI: 10.1039/C0OB01133A

Both articles are FREE to download until the end of June.

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Cascade reactions and multiple rings – OBC emerging area

Cascade or domino processes have become one of the Holy Grails in organic synthesis. They allow the sequential formation of multiple new bonds and therefore, the one-pot synthesis of new and complex organic molecules. 

The formation of new cyclic frameworks in a controlled-one synthetic operation is almost a dream come true for synthetic chemists due to the complexity and challenging structure of these heterocycles.

In this review article, Edward Anderson, at Oxford University, gives us a selective overview of cascade reactions as applied to natural product synthesis. We invite you to download it and read this excellent accounting of recent cascade-based polycyclic reactions towards the synthesis of natural products.

Cascade polycyclisations in natural product synthesis
Edward A. Anderson
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C1OB05212H, Emerging Area

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Catalytic asymmetric C-H insertions-OBC perspective

Asymmetric catalytic intramolecular carbon-hydrogen insertion reactions are pivotal reactions in the world of organic chemistry and there is a considerable amount of literature on this topic.

Michael Doyle and his colleagues at University of Maryland, have now written a very original and different review on the catalytic C-H insertion process in comparison with other approaches for the synthesis of selected synthetic targets, lactones and lactams, which have been of biological or medicinal interest. They discuss these well-defined targeted molecules for which there have been multiple examples of their synthesis. They conclude by saying that the catalytic route through chiral dirhodium(II) carboxamidates is the most appropriate method for the stereoselective carbon–hydrogen insertion reactions that produce biologically relevant lactones and lactams.

If you want to find out more about the different synthetic approaches and the advantges of using one over the other, download this very interesting review.

Intramolecular catalytic asymmetric carbon–hydrogen insertion reactions. Synthetic advantages in total synthesis in comparison with alternative approaches
Michael P. Doyle, Maxim Ratnikov and Yu Liu
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB00698J, Perspective

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HOT: Monitoring intracellular copper levels in living cells

Copper is an essential trace element in the physiology of living organisms as many critical proteins and enzymes contain copper in their active sites or/and require copper for their activities.
Disruption of copper levels in cells can cause diseases such as Menkes syndrome, Wilson’s disease, amyotrophic lateral sclerosis and Alzheimer’s. Therefore, the quantitative detection of intracellular copper could help with the understanding of its complex physiological and pathological roles.

Unlike other trace metals such as zinc, iron, chromium and mercury, which can be successfully detected with rhodamine-based fluorescence probes, the detection of copper has proven to be more challenging and the development of satisfactory fluorescent probes needs addressing.

Bao-Xiang Zhao, Jun-Ying Miao and colleagues at Shandong University in China have now developed a rhodamine chromene-based fluorescence probe to monitor the intracellular levels of copper in living cells. The probe switches to a highly fluorescent complex upon coordination with copper under physiological conditions in a very sensitive and selective manner and facilitates the naked-eye detection of the metal.

If you want to learn more about this satisfactory fluorescent probe I invite you to download this paper that is free to access until 15th June.

Synthesis, crystal structure and living cell imaging of a Cu2+-specific molecular probe
Wei-Yong Liu, Hai-Ying Li, Bao-Xiang Zhao and Jun-Ying Miao
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C1OB05358B

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HOT: One electron oxidation of substituted ferrocenes

How can the structure of short-lived N-oxyl radicals influence its electron transfer (ET) properties?

Osvaldo Lanzalunga and his team at Sapienza Universita di Roma and Istituto CNR di Metodologie Chimiche (IMC-CNR) provide some answers to this question in this OBC HOT paper.

They study the kinetics of the one electron oxidation of substituted ferrocenes by a series of N-oxyl radicals in acetonitrile and determine self-exchange reorganization energy values.
They conclude by saying that ‘even small modifications of the structure of the N-oxyl radicals lead to signifiant variation of the self-exchange reorganization energy values.’

If you want to read more about these results, you can download the paper for free until 8th June.

This paper is part of the Free Radical collection of papers in memory of Athel Beckwith, which will be published at the end of May. Watch this space.

One-electron oxidation of ferrocenes by short-lived N-oxyl radicals. The role of structural effects on the intrinsic electron transfer reactivities
Enrico Baciocchi, Massimo Bietti, Claudio D’Alfonso, Osvaldo Lanzalunga, Andrea Lapi and Michela Salamone
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB01257B

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