Organic & Biomolecular Chemistry Blog

Leishmania is a terrible disease transmitted by the bite of a sandfly.  Tackling it has been given priority by the WHO, especially as co-infection with HIV has been identified.  Many current treatments are costly, have serious side effects and more worryingly drug resistance has been reported even in the most recent drugs.  Therefore identifying new therapeutic targets to combat this disease is imperative.

Patrick Steel and a team from Durham University have targeted the membrane bound enzyme inositol phosphorylceramide synthase (IPCS)  – which is essential for the survival of Leishmania species.  They synthesised a series of ceramide analogues, changing the sphingosine tail, N-acyl unit and the degree of hydroxylation to explore the enzyme active site.  The analogues were assayed against Leishmania major IPCS to determine the degree of inhibition and a mechanism of action was subsequently proposed.

Read about their findings here – the article is free to access for 4 weeks:

Exploring Leishmania major Inositol Phosphorylceramide Synthase (LmjIPCS): Insights into the ceramide binding domain
John G. Mina, Jackie A. Mosely, Hayder Z. Ali, Paul W. Denny and Patrick G. Steel
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB00871K

Ribavirin is a nucleoside drug used to treat RNA viral infections such as Hepaptitis C, which interferes with RNA metabolism required for viral replication. But its efficiency is relatively low, so in a HOT article just published, Yang He and colleagues at Sichuan University report the synthesis of two new nucleosides and their improved anti-viral activity.

He’s nucelosides contain structural features of two naturally occurring components of RNA (guanine and cytosine). This unique feature allows it to interfere with the RNA virus via hydrogen bond pairing with either guanine or cytosine, as well as allowing it to be recognised by viral enzymes more efficiently than ribavirin.   

 If you want to find out more about these interesting bio-active nucleosides download the article now! It’s free to access until the 18th February.

Synthesis of Janus type nucleoside analogues and their preliminary bioactivity 
Hao-Zhe Yang, Mei-Ying Pan, Da-Wei Jiang and Yang He
Org. Biomol. Chem., 2011, DOI: 10.1039/C0OB00495B

Poul Nielsen and his group at University of Southern Denmark describe the synthesis of new double-headed nucleosides, using the CuAAC reaction, and their influence on the stability of the hybridization of oligonucleotides.

In this HOT paper they describe a new type of nucleosides that are able to stabilize three-way junctions. If you want to find out more about these interesting stabilising contacts download the article, which is free to access until the 8th February.

The synthesis of double-headed nucleosides by the CuAAC reaction and their effect in secondary nucleic acid structures
Anna S. Jørgensen, Khalil I. Shaikh, Gerald Enderlin, Elise Ivarsen, Surender Kumar and Poul Nielsen
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB00438C

To give you a better overview on Nielsen’s previous research, we have outlined below a collection of their latest OBC published papers. Enjoy!

Stabilisation of nucleic acid secondary structures by oligonucleotides with an additional nucleobase; synthesis and incorporation of 2′-deoxy-2′-C-(2-(thymine-1-yl)ethyl)uridine
Søren Ljungberg Pedersen and Poul Nielsen
Org. Biomol. Chem., 2005, 3, 3570-3575
DOI: 10.1039/B510167K

Synthesis and modelling of DNA junction and minor groove zipper motifs incorporating the double-headed nucleoside 5′(S)–C-(thymine-1-ylmethyl)thymidine
Mikkel S. Christensen, Charlotte M. Madsen and Poul Nielsen
Org. Biomol. Chem., 2007, 5, 1586-1594
DOI: 10.1039/B700852J

Nucleic acid secondary structures containing the double-headed nucleoside 5′(S)-C-(2-(thymin-1-yl)ethyl)thymidine
Charlotte Andersen, Pawan K. Sharma, Mikkel S. Christensen, Signe I. Steffansen, Charlotte M. Madsen and Poul Nielsen
Org. Biomol. Chem., 2008, 6, 3983-3988
DOI: 10.1039/B810930C

Inhibition of angiotensin converting enzyme (ACE) is generally used as one of the methods for the treatment of hypertension. ‘Oxidative stress’ is another disease state caused by an imbalance in the production of oxidants and antioxidants. Hypertension and oxidative stress may be interdependent. Therefore, ACE inhibitors having antioxidant properties are considered beneficial for the treatment of hypertension.

Bhaskar J. Bhuyan and Govindasamy Mugesh at the Indian Institute of Science in Bangalore, India, synthesise in this paper a number of selenium analogues of captopril, an ACE inhibitor used as an antihypertensive drug. These analogues not only inhibit ACE activity but also effectively scavenge peroxynitrite, a strong oxidant found in vivo.

Read this paper which is free to access until the 4th February. The referees strongly recommended it and the editorial office as well.

Synthesis, characterization and antioxidant activity of angiotensin converting enzyme inhibitors Bhaskar J. Bhuyan and Govindasamy Mugesh
 Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB00823K, Paper