Organic & Biomolecular Chemistry Blog

PBDs (pyrrolo[2,1-c][1,4]benzodiazepines) and their interaction with DNA is an area of active research.

PBDs belong to a family of biologically active an DNA-interactive antibiotics having unique mechanism of action compared with other DNA-binding agents. Up until now, there have been several reports in literature suggesting that PBD-DNA adduct formation might be reversible; however, no evidence of this reversibility had been reported.

For the first time, in this paper, David Thurston and colleagues at the School of Pharmacy at University of London, investigate the adduct formation of PBDs with DNA and its reversibility using HPLC/MS methodology and polarised light spectroscopy.

Read about some of their findings in this OBC HOT paper which is free to access until the 22nd February.

Observation of the reversibility of a covalent pyrrolobenzodiazepine (PBD) DNA adduct by HPLC/MS and CD spectroscopy
Khondaker M. Rahman, Colin H. James and David E. Thurston
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB00762E, Paper

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

Michael D. Threadgill and coworkers at University of Bath report a very interesting synthesis of 4,5-disubstituted isoquinolin-1-ones and their biological evaluation against PARP-2.

This paper is specially relevant because of the difficulties of working with this class of compound such as insolubility and lack of reactivity. This is a HOT paper that will be free to access until 6th December.

A very neat synthesis relevant for the synthetic and medicinal chemistry communities.

Synthesis of 4-alkyl-, 4-aryl- and 4-arylamino-5-aminoisoquinolin-1-ones and identification of a new PARP-2 selective inhibitor
Peter T. Sunderland, Archana Dhami, Mary F. Mahon, Louise A. Jones, Sophie R. Tully, Matthew D. Lloyd, Andrew S. Thompson, Hashim Javaid, Niall M. B. Martin and Michael D. Threadgill
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB00665C,