RSC Medicinal Chemistry Blog

RSC US Roadshow 2012 – Week 4: North East

04 May 2012

MedChemComm Editor Richard Kelly will be visiting several North East universities next week as part of the RSC US Roadshows 2012.

Week 4 sees the Royal Society of Chemistry visiting four universities in Pennsylvania and New York:

May 7th – University of Pittsburgh

May 8th – Pennsylvania State University

May 10th – University of Pennsylvania

May 11th – Columbia University

Read more about the US roadshows 2012:

Starting in mid April 2012, RSC Publishing has been touring the United States of America to share more than 170 years experience of publishing in the chemical sciences. Sixteen universities across the country are hosting these one-day events, which are open to all members of the hosting institute.

Attendees have the opportunity to explore RSC’s apps on mobile devices and meet informally with RSC editors. Lunchtime discussion groups explore reading habits and opportunities in the 21st century and an afternoon seminar give an insight into the world of scholarly publishing, with tips on how to get published in high impact journals. A demonstration of ChemSpider, and a guest lecture from an RSC associate editor or board member are available at many of the roadshows.

Follow the RSC Roadshows on Twitter – just look for #RSC2012.

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Potent inhibition of Ca2+-dependent activation of calpain-1 on the cover of issue 5

03 May 2012

By James Anson.

The cover of MedChemComm issue 5 is by Rudolf K. Allemann et al., whose concise article presents the synthesis of a series of monohalide mercaptoacrylic acid derivatives, and looks at the structure activity relationship in order to investigate the ability of these molecules to inhibit the Ca²⁺ activation of calpain-1, which is linked with tissue inflammation.

Potent inhibition of Ca²⁺-dependent activation of calpain-1 by novel mercaptoacrylates
Sarah E. Adams, Christian Parr, David J. Miller, Rudolf K. Allemann and Maurice B. Hallett
Med. Chem. Commun., 2012,
DOI: 10.1039/C2MD00280A

As with all our covers, this work will be free to access for the next 6 weeks.

You may also be interested in the 3 reviews in the issue on how enantiomeric pairs reveal that key medicinal chemistry parameters vary more than simple physical property based models can explain, small-molecule inhibitors of dimeric transcription factors and Gd(III) chelates for MRI contrast agents.

Find the entire issue right here

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Review: Aminoacyl tRNA synthetases as targets for antibiotic development

30 Apr 2012

By James Anson.

In this review from MedChemComm‘s forthcoming Natural Product themed issue, Vinayak Agarwal and Satish K. Nair (University of Illinois at Urbana-Champaign) review a number of small molecule natural products, that target aminoacyl tRNA synthetases, which are available for development into useful antibiotics. In particular Agarwal and Nair focus on three different chemical classes:

Molecules derived from polyketide precursors
Molecules that occur as phosphoramidate conjugates
Promising synthetic molecules with distinct modes of action to molecules of class 1 and 2

The factors that undermine the broad-based use of some of these molecules as effective antibiotics in humans are also discussed, as well as strategies to aid in directing development of derivatives with improved pharmacological properties.

Aminoacyl tRNA synthetases as targets for antibiotic development
Vinayak Agarwal and Satish K. Nair
Med. Chem. Commun., 2012,
DOI: 10.1039/C2MD20032E

We will be bringing you more examples of work from this themed issue, guest edited by Professor Christopher T. Walsh andDr Sylvie Garneau-Tsodikova, over the next few weeks so make sure you check back for more.

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Review: Discrete acyltransferases involved in polyketide biosynthesis

18 Apr 2012

By James Anson.

In this review Ewa Maria Musiol and Tilmann Weber at Eberhard Karls University, Tübingen present a summary of genetically and biochemically characterized in trans active ATs, which supply polyketide synthases assembly lines with building blocks and thus, might influence the polyketide structure by their substrate selectivity.

Included in this review are discussions on:

MmpC involved in mupirocin biosynthesis
OzmM and OzmC involved in oxazolomycin biosynthesis
RhiG involved in rhizoxin biosynthesis
VirI involved in virginiamycin biosynthesis
TaV involved in myxovirescin biosynthesis
BryP involved in bryostatin biosynthesis

…. and many more.

Discrete acyltransferases involved in polyketide biosynthesis
Ewa Maria Musiol and Tilmann Weber
Med. Chem. Commun., 2012,
DOI: 10.1039/C2MD20048A

This review is part of our forthcoming themed issue on Natural Products, guest edited by Professor Christopher T. Walsh and Dr Sylvie Garneau-Tsodikova – keep checking back for more hot research in this theme.

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Nanoscale engineering of wound beds

13 Apr 2012

By Nathalie Horner.

A collagen-binding peptide with applications in wound healing has been developed by scientists in the US. The peptide is able to invade the strands of collagen, forming a strong and stable non-covalent bond at room temperature. Pendant drug molecules could be attached to the peptide and anchored at the wound site to aid wound healing…

Read the full article at Chemistry World, or read the Organic & Biomolecular Chemistry paper:

Peptides that anneal to natural collagen in vitro and ex vivo
Sayani Chattopadhyay, Christopher J. Murphy, Jonathan F. McAnulty and Ronald T Raines
DOI: 10.1039/C2OB25190F

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Review: Biosynthetic medicinal chemistry for lead advancement

12 Apr 2012

By Marie Cote, Deputy Editor.

‘Natural products are an unsurpassed source of lead structures for drug discovery. However, these molecules, many of which fall into the beyond-rule-of-5 chemical space, are often difficult to optimize by chemical means because of their complex structures.’, explains Frank E. Koehn (Pfizer, Natural Products, Oncology Worldwide Medicinal Chemistry Groton, USA).

In this MedChemComm review article, Frank E. Koehn provides the reader with an overview on biosynthesis-oriented strategies to access analogues of natural products, which would be unattainable by chemical semisynthesis. Five relevant examples of distinct drugs, namely:

salinosporamide
geldanamycin
FK506
rapamycin
epothilone

are described, for which libraries of analogues have been prepared via biosynthetic engineering approaches and which are under intensive biological investigation or already in clinical use.

This review is part of our forthcoming themed issue on Natural Products, guest edited by Professor Christopher T. Walsh and Dr Sylvie Garneau-Tsodikova – keep checking back for more hot research in this theme:

Biosynthetic medicinal chemistry of natural product drugs
Frank E. Koehn
Med. Chem. Commun., 2012, Review Article

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The Discovery of Brilinta – Daring to be Different

10 Apr 2012

By Marie Cote, Deputy Editor.

You are invited to attend the Royal Society of Chemistry’s Healthcare Innovation event on Wednesday 18 April, 5.30 pm at The Chemistry Centre, Burlington House, London, W1J 0BE

The Discovery of Brilinta – Daring to be Different
Dr John Dixon CChem FRSC

Over the last 30 years, improvements in healthcare and technology have led to an increase in life expectancy and a general rise in the level of health. The UK has for decades been a world leader in medicines discovery and research. The Discovery of Brilinta is a unique example of UK drug discovery excellence and is a potential blockbuster for the treatment of antithrombotic conditions for use in reducing heart attacks and cardiovascular death.
Our keynote speaker, Dr John Dixon will outline aspects of the discovery of Brilinta (ticagrelor) from the chemical starting point of ATP leading to a complex carbocyclic nucleoside analogue which was developed into a immediate release tablet. Ticagrelor is a reversible, selective P2Y12-receptor antagonist which was finally approved by the FDA in 2011 and is marketed in most countries.

The RSC has organised this event to highlight the pivotal role played by medicinal chemists in the discovery of Brilinta as well as provide a discussion forum for anyone who has an interest in the future of UK drug discovery. The nature of drug discovery is changing and is under considerable pressure due to escalating R&D costs and high drug discovery failure rates. Will it be possible to peruse complex drug discovery programmes in a fragmented environment?
I do hope you are able to join us for what will prove to be a very exciting and interesting lecture and discussion. Refreshments are available from 5.30 pm. The lecture will start at 6.00 pm and will be followed by a wine reception.

Please register here by 13 April or RSVP to sciencepolicy@rsc.org. Spaces are limited and will be allocated on a first come, first served basis.

About the Keynote speaker:
Dr John Dixon has 36 years experience of medicinal chemistry and drug discovery. He was Head of Medicinal Chemistry for 20 years at Fisons, Vice President of Pre Clinical R&D at Astra Charnwood for 4 years and Vice President of Drug Discovery at AstraZeneca Charnwood for 9 years. As VP of AstraZeneca Charnwood he was involved in development of 35 candidate drugs, particularly in the respiratory area. In July 2008, John became Director of JD International Consulting Ltd, an independent consultancy working with pharmaceutical and biotech organisations around the world. John is a Fellow of the Royal Society of Chemistry and Member of the American Chemical Society and has served on several professional and academic advisory committees.

Posted on behalf of the Conferences and Events team

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Review: Gd(III) chelates for MRI contrast agents

02 Apr 2012

By Marie Cote, Deputy Editor.

Kai-Hsiang Chuang and Chang-Tong Yang from the Singapore Bioimaging Consortium, A*STAR provide a timely review on the major developments of Gd(III) chelates as MRI contrast agents, from high relaxivity to ‘‘smart’’, from blood pool to blood–brain barrier.

The review covers:

Relaxivity of Gd(III) based MRI contrast agents
Smart contrast agents (pH-, metal ion-, enzyme- ; small biomolecule-activated)
Blood pool contrast agents (non-covalent binding to plasma proteins, polymeric and dendrimeric contrast agents)
Blood–brain barrier permeable contrast agents

Should your interests lie in coordination chemistry, polymer and supramolecular chemistry, medicinal chemistry, spectroscopy, biology or radiology, this review is for you!

Gd(III) chelates for MRI contrast agents: from high relaxivity to “smart”, from blood pool to blood–brain barrier permeable
Chang-Tong Yang and Kai-Hsiang Chuang
Med. Chem. Commun., 2012, Advance Article
DOI: 10.1039/C2MD00279E, Review Article

Why not also view our 2011 collection of topical review articles, across the full range of the journal scope, here.

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Computational screening of protein kinases on the cover of MedChemComm issue 4

28 Mar 2012

By James Anson.

The cover of this month’s issue of MedChemComm features work from Bonnet et al. on discriminating Type II kinase inhibitors from a large number of Type I and other decoy ligands taken from the MOE kinase and DUD databases. Have a read, it’s FREE to access for 6 weeks.