skip to main |
skip to sidebar
Bioorthogonal Profiling of Protein Methylation Using Azido Derivative of S-Adenosyl-L-methionine, Minkui Luo, et al, J. Am. Chem. Soc. 2012, 134, 5909-5915
dx.doi.org/10.1021/ja2118333
A few key points:
1. Protein methytransferase transfers methyl group from S-Adenosyl-L-methionine (SAM) to specific proteins.
2. Selective mutation of a transferase allows its acceptance of modified azido-SAM.
3. Instead of methyl group, the azido-R group was transferred to specific proteins in cells with above SAM transferase.
4. Copper-free Click chemistry and MS reveal the identity of the specific methylated protein.
5. Therfore, methyltransferase - target protein link is established.
Active Motif offers research kits, assays, and the TimeLogic® biocomputing systems. Now it has extended to click chemistry reagents such as Chromeo™ Dyes for bioorthogonal labeling.
Active Motif was founded in 1999 and is headquartered in Carlsbad, California, and has international offices in Tokyo, Japan and Brussels, Belgium.
A collection of vendors with similar offerings was compiled previously:
Click Chemistry: Reagent Vendors Matter (February 8, 2010)
http://www.mit.edu/press/2010/500k-lemelson.html
By MIT press release of June 2nd, 2010, Carolyn Bertozzi was selected for the prestigious 2010 $500,000 Lemelson-MIT Prize.
Her contribution in the field of biotechnology includes: Bioorthogonal reactions, or biocompatible click chemistry, or the copper-free version; Glycobiology innovations and imaging glycans; Genetically-encoded aldehyde tags; Cell nanoinjector.
The bioorthogonal click chemistry yielded in vivo imaging of sugar molecules in live animals. The aldehyde tag technology is the basis for the company Redwood Bioscience.
Her response? "This came completely out of the sky - it's totally stunning news."
Chem. Soc. Rev., 2010 DOI: 10.1039/b901970g
Carolyn Bertozzi et al clearly defined the bioorthognal click chemistry. They used this figure to illustrate a general bioorthogonal reaction. Best described: "we must first look at an organic chemistry textbook and remove any reaction that is sensitive to water. Second, with an abundant supply of thiols and amines in the cell, we must also remove reagents that are prone to nucleophilic attack. Third, because of the reducing environment in the cytosol, we have to remove reactions that are sensitive to redox chemistry. If a reaction requires heat (above 37 °C), pressure, or high concentrations to work then it is also unacceptable. Lastly, some functionalities can be digested by cellular enzymes that have an ase in their name (e.g., esterase, phosphatase, sulfatase, etc.). Add reagent toxicity to this list and you will find a select few reactions that remain viable for performance in living systems."
Indeed one needs to be very picky in picking a good bioothogonal reaction from the already- small click chemistry tool box. The review covers the most viable reactions up-to-date, lists their pros and cons, and potentials. The chemistry aspects are detailed, with great insights and perspectives from a mechanistic point of view.
And did I mention the secret - go back to the old dusty organic chemistry toolbox and find treasures, such as click chemistry?
Posts
