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Archive for the ‘Reviews’ Category

Review: Labile natural products

28 May 2012

Natural product isolation has developed as techniques have advanced e.g. improvements in chromatographic methodologies, however isolating labile natural products remains a large difficulty due to their inherent instability. Such is their instability that even the removal of solvents in vacuo, a common step during isolation, can destroy them. As such new careful isolation techniques are needed to offer access to new natural products and their biosynthetic intermediates.

In this review Toshiyuki Wakimoto and Ikuro Abe discuss the current success in isolating labile natural products. Examples highlighted by Wakimoto and Abe include:
–Red pigments from a hippopotamus
-Labile polyketides from filamentous fungi
-Cyclopropene carboxylic acids from mushrooms
-Aziridine carboxylic acids from mushrooms
-Furan fatty acids from mussels

Labile natural products
Toshiyuki Wakimoto and Ikuro Abe
DOI: 10.1039/C2MD20016C

This review is part of MedChemComm’s Natural Products themed issue. Check out the rest of the articles appearing in this issue today…..

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Review: Latent antibiotics and the potential of the arylomycins for broad-spectrum

18 May 2012

Antibiotic resistance in bacterial pathogens is becoming increasingly common and so there is a need for the development of new antibiotics, which act in novel ways, to counter-act this. In this review, featuring in MedChemComm‘s Natural Products themed issue, Yun Xuan Tan and Floyd E. Romesberg (The Scripps Research Institute) review the arylomycins, the recently discovered class of natural product antibiotics that inhibit bacterial type I signal peptidase (SPase), an endoprotease that is required for the translocation of most proteins across the cytoplasmic membrane.

Tan and Romesberg assess how the total synthesis of several members of this family of natural products has allowed studies which show that their spectrum of activity is broader than previously thought. The discussion goes on to how the arylomycins may represent “latent” antibiotics, antibiotics that have scaffolds that once had potent and broard-spectrum activity, and how these are more likely to be optimised to regain this activity than other scaffolds that have never been antibiotics.

Read the full review to find out all the facts

If you liked that, then take a look at the other published articles. We’re sure you will find something that will grab your attention.

Latent antibiotics and the potential of the arylomycins for broad-spectrum antibacterial activity
Yun Xuan Tan and Floyd E. Romesberg
Med. Chem. Commun., 2012, DOI: 10.1039/C2MD20043K

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Review: Aminoacyl tRNA synthetases as targets for antibiotic development

30 Apr 2012

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

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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Review: Biosynthetic medicinal chemistry for lead advancement

12 Apr 2012

‘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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Review: Gd(III) chelates for MRI contrast agents

02 Apr 2012

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

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.

Targeting the inactive conformation of protein kinases: computational screening based on ligand conformation
Pascal Bonnet, Daniel Mucs and Richard A. Bryce
DOI: 10.1039/C1MD00256B

This issue also contains three reviews which you may find interesting:

Understanding and overcoming aminoglycoside resistance caused by N-6′-acetyltransferase
Kenward Vong and Karine Auclair
DOI: 10.1039/C2MD00253A

β-Lactams and β-lactones as activity-based probes in chemical biology
Thomas Böttcher and Stephan A. Sieber
DOI: 10.1039/C2MD00275B

The MEP pathway and the development of inhibitors as potential anti-infective agents
Ian Hale, Paul M. O’Neill, Neil G. Berry, Audrey Odom and Raman Sharma
DOI: 10.1039/C2MD00298A

View all this and much more HERE!

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Review of the biosynthetic MEP pathway and potential anti-infective agents

13 Mar 2012

Audrey Odom, Raman Sharma and colleagues present a review examining the enzymes in the biosynthetic non-mevalonate (MEP) pathway from a detailed medicinal chemistry and structural biology perspective. The MEP pathway is utilised by plants but is absent in mammalian systems, making it a very attractive target for the development of potential next generation antimicrobial chemotherapeutics as well as novel herbicides.

Want to find out more about this pathway and its potential agents? You’re just a click away….

The MEP pathway and the development of inhibitors as potential anti-infective agents
Ian Hale, Paul M. O’Neill, Neil G. Berry, Audrey Odom and Raman Sharma
Med. Chem. Commun., DOI: 10.1039/C2MD00298A

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Review article on small-molecule inhibitors of dimeric transcription factors: a challenging area

13 Mar 2012

Disruption of protein–protein or protein–DNA interactions involved in transcriptional machinery using small molecules poses a real challenge owing to several factors, including: the large interfacial areas involved, the lack of obvious binding sites, and the large free energy of association between the interfaces.

However, in recent years there has been considerable success in the dimeric transcription factor disruption using small molecules. Steven Fletcher and co-workers at University of Maryland School of Pharmacy, provide a review of the progress made in this area since 2008.

This review covers:

Inhibitors of STAT3
Inhibitors of c-Myc
Inhibitors of AP-1
Inhibitors of HIF-1

Small-molecule inhibitors of dimeric transcription factors: Antagonism of protein–protein and protein–DNA interactions
Jeremy L. Yap, Jay Chauhan, Kwan-Young Jung, Lijia Chen, Edward V. Prochownik and Steven Fletcher
Med. Chem. Commun., 2012,
DOI: 10.1039/C2MD00289B, Review

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Review article on β-lactams and β-lactone probes for chemical biology

28 Feb 2012

β-lactams and β-lactone probes for chemical biology Thomas Böttcher and Stephan A. Sieber here review the use of β-lactams and β-lactones for activity-based protein profiling. ABPP uses small molecules to target the active site of specific enzymes and is useful for understanding protein targets of natural products, drugs or synthetic libraries. β-Lactams and β-lactones are ideal probes for ABPP due to their so-called ‘privileged structures’, i.e. they have a core scaffold that can be recognised by a wide range of enzyme classes and can be ‘fine-tuned to obtain customized target selectivity’.

Take a look at this detailed review, which provides an update to of the field of activity-based β-lactam and β-lactone probes and their applications in chemical biology:

β-Lactams and β-lactones as activity-based probes in chemical biology
Thomas Böttcher and Stephan A. Sieber
Med. Chem. Commun., 2012, Advance Article
DOI: 10.1039/C2MD00275B

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