June 2010

JBC Minireview Explores Another Scientific Intersection


Throughout its 105-year history, the Journal of Biological Chemistry has stayed true to its title and presented numerous papers that use chemistry to understand biological processes; in fact, articles that feature new chemical reagents or small molecule enzyme inhibitors generally are among the journal’s most-cited papers.

Therefore, even though chemical biology— defined as the use of chemical tools and techniques to advance a molecular understanding of biology— has emerged as a unique discipline in the molecular life sciences, with its own set of journals and meetings, it finds itself highly intertwined with biological chemistry. In effect, these two disciplines need each other.

To highlight this perhaps inseparable connection, the JBC put out a new minireview series in April, titled “Chemical Biology Meets Biological Chemistry.”

Coordinated by JBC Associate Editor Joel M. Gottesfeld and Benjamin F. Cravatt, this series features six minireviews that emphasize the importance of uniting synthetic chemistry with biochemistry in the study of complex biological processes. The minireviews highlight both the application of chemical techniques toward understanding life processes at the molecular level and the development of synthetic compounds either as tools for research or therapies for disease.

In the first minireview, Lori W. Lee and Anna K. Mapp describe the development of synthetic small molecules to control transcription in eukaryotic cells; one notable example mentioned is p53, whose misregulation is involved in half of all cancers, yet, the molecule still remains a bit of a mystery.

Next, Travis S. Young and Peter G. Schultz describe efforts to introduce non-natural amino acids into proteins, for example, residues with side chains that contain fluorophores, post-translational modifications, metal-binding ligands and photocross-linking reagents.

Champak Chatterjee and Tom W. Muir, meanwhile, describe techniques such as native chemical ligation and related synthetic methods used to generate histones with unique post-translational modifications to better probe chromatin structure and function.

In the fourth minireview, Gabriel M. Simon and Cravatt describe activity-based protein profiling, a technique in which reactive chemical probes are used to identify the targets of small molecule drugs, characterize members of enzymes families or screen for inhibitors.

2010 Meeting Compendia

If you didn’t get copies of the 2010 ASBMB Annual Meeting Compendia, you can still download them. Titles include:
• Initiating DNA Replication and Transcription
• Protein Synthesis
• Drug Discovery and Design
• Genomes, Proteomes and Development
• Nutrient Sensing & Signaling
• Lipids: On the Move
• Building Protein Complexes

Next, Kanak Raina and Craig M. Crews describe chemical alternatives to RNA interference to probe the function of selected proteins in living cells, for example sending specific proteins to the proteasome by targeted ubiquitination of the protein of interest. These methods might overcome RNAi limitations like off-target effects and difficulty in dealing with long-lived proteins.

In the final minireview, Maurizio Renna, Maria Jimenez-Sanchez, Sovan Sarkar and David C. Rubinsztein describe a related approach, using chemical inducing agents to promote the autophagy and clearance of protein aggregates that underlie neurodegenerative diseases — this could have tremendous therapeutic benefits.

These six minireviews may only provide a small sampling of the diverse field of chemical biology, but they certainly should convey the excitement surrounding this dynamic area and the great potential that chemical applications hold in solving important biological problems.

Look for future minireview series exploring cross-disciplinary topics, including a series on antibiotic synthesis and one on single-molecule studies. 

Nick Zagorski (nzagorski@asbmb.org) is a science writer at ASBMB.

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