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Will the Correct Structure of Taxol PLEASE STAND UP!!!!

01 Jul

Recently David Bradley blogged on Spinneret about the application of coherent anti-Stokes Raman scattering microscopy to evaluate a new approach to the controlled released of the drug Taxol. I’m sure all chemists have heard of Taxol at this point? It’s got a great history and that is discussed on many other places so I’m not going to belabor that. What Taxol is, for the purpose of this rant, is a nice structure…lots of stereochemistry and not simple to draw (there are certainly worse of course.) The structure is shown below.

Structure of Taxol

While thinking through the concept of providing a central resource for Natural Product chemists to deposit and access information of value to their community I started looking at Taxol as an example of the type of complexity we’d be dealing with in terms of structural complexity during the deposition process. My question was how well would it be dealt with already…

So, I did a few searches….

I searched the InChI generated from the structure shown above in Google. I received three hits on this search including

1) Goodman’s Group in Cambridge – check out the page..uses Jmol and is a good example of how nice this tool is. Click and rotate the molecule! JMol will show up on ChemSpider soon.

2) A link into Drugbank

I also used PubChem, Emolecules and ChemSpider to provide me links into their various data sources. The search was simple..I searched on the compound name of Taxol in each system since I was trying to emulate a search that a user would do…search for the compound by name and identify the “correct structure”. Some interesting results…

1) PubChem: 37 hits total with the top 4 being “Taxol” hits rather than Taxol analogs. The structures are shown below.

Taxol on PubChem

Consistent masses…of the four, three have the same mass one doesn’t. The FIRST in the list matches what we believe is the correct structure for Taxol based on matching the InChIs with that of the structure above.

2) Emolecules : I received two results…sometimes 7 hits, sometimes 4…including the issue observed in PubChem of one Taxol not having the correct mass. I cannot find InChI codes on Emolecules (though they might be there) so cannot confirm which is the right Taxol or even whether it is on there. Since a lot of the data includes PubChem deposition I believe it will be there but I searched on the two PubChem links for CID 36314 (the first structure in the PubChem image above) and could not find that link (here or here). Again…I think it’s there but don’t know where.

3) ChemSpider : 4 hits obtained, one with the Mw issue shown in Emolecules and PubChem and the correct Taxol being record ID 390039. The first record is the correct Taxol as evidenced by the InChI match as well as the link back to PubChem 36314 as shown below.

ChemSPider to PubCHem link

Confused yet??? Here’s what it means …the data quality of Taxol across many databases is in question. Online resources, including our own (!) abound with errors and while there are ongoing discussions about scraping data from this source and that using robots are appropriate in technology WHO is going to ensure quality? We would like to hold ChemSpider up as a quality resource of course…as would our other colleagues at PubChem, Emolecules and a majority of data source providers. But..as I’ve just shown…there are issues.

We ARE curating our data…thankfully the chemistry community is helping. Together we have a chance to make a difference.

Last night we received a comment from a curator stating “This structure is not correct for bis(3-ethylhexyl) phthalate. Also, on a somewhat related note, I couldn’t find an entry for bis(2-ethylhexyl) phthalate, which, in terms of chemical production, is probably the most abundant of all phthalates.” for record 556873. How RIGHT he is. A lot of us have the same problem! See here

Issues like this can be caught with name to structure conversion algorithms and comparisons but the work must be done…until then, manual curation of the database is necessary. Thanks to those helping!

 

About tony

Antony (Tony) J. Williams received his BSc in 1985 from the University of Liverpool (UK) and PhD in 1988 from the University of London (UK). His PhD research interests were in studying the effects of high pressure on molecular motions within lubricant related systems using Nuclear Magnetic Resonance. He moved to Ottawa, Canada to work for the National Research Council performing fundamental research on the electron paramagnetic resonance of radicals trapped in single crystals. Following his postdoctoral position he became the NMR Facility Manager for Ottawa University. Tony joined the Eastman Kodak Company in Rochester, New York as their NMR Technology Leader. He led the laboratory to develop quality control across multiple spectroscopy labs and helped establish walk-up laboratories providing NMR, LC-MS and other forms of spectroscopy to hundreds of chemists across multiple sites. This included the delivery of spectroscopic data to the desktop, automated processing and his initial interests in computer-assisted structure elucidation (CASE) systems. He also worked with a team to develop the worlds’ first web-based LIMS system, WIMS, capable of allowing chemical structure searching and spectral display. With his developing cheminformatic skills and passion for data management he left corporate America to join a small start-up company working out of Toronto, Canada. He joined ACD/Labs as their NMR Product Manager and various roles, including Chief Science Officer, during his 10 years with the company. His responsibilities included managing over 50 products at one time prior to developing a product management team, managing sales, marketing, technical support and technical services. ACD/Labs was one of Canada’s Fast 50 Tech Companies, and Forbes Fast 500 companies in 2001. His primary passions during his tenure with ACD/Labs was the continued adoption of web-based technologies and developing automated structure verification and elucidation platforms. While at ACD/Labs he suggested the possibility of developing a public resource for chemists attempting to integrate internet available chemical data. He finally pursued this vision with some close friends as a hobby project in the evenings and the result was the ChemSpider database (www.chemspider.com). Even while running out of a basement on hand built servers the website developed a large community following that eventually culminated in the acquisition of the website by the Royal Society of Chemistry (RSC) based in Cambridge, United Kingdom. Tony joined the organization, together with some of the other ChemSpider team, and became their Vice President of Strategic Development. At RSC he continued to develop cheminformatics tools, specifically ChemSpider, and was the technical lead for the chemistry aspects of the Open PHACTS project (http://www.openphacts.org), a project focused on the delivery of open data, open source and open systems to support the pharmaceutical sciences. He was also the technical lead for the UK National Chemical Database Service (http://cds.rsc.org/) and the RSC lead for the PharmaSea project (http://www.pharma-sea.eu/) attempting to identify novel natural products from the ocean. He left RSC in 2015 to become a Computational Chemist in the National Center of Computational Toxicology at the Environmental Protection Agency where he is bringing his skills to bear working with a team on the delivery of a new software architecture for the management and delivery of data, algorithms and visualization tools. The “Chemistry Dashboard” was released on April 1st, no fooling, at https://comptox.epa.gov, and provides access to over 700,000 chemicals, experimental and predicted properties and a developing link network to support the environmental sciences. Tony remains passionate about computer-assisted structure elucidation and verification approaches and continues to publish in this area. He is also passionate about teaching scientists to benefit from the developing array of social networking tools for scientists and is known as the ChemConnector on the networks. Over the years he has had adjunct roles at a number of institutions and presently enjoys working with scientists at both UNC Chapel Hill and NC State University. He is widely published with over 200 papers and book chapters and was the recipient of the Jim Gray Award for eScience in 2012. In 2016 he was awarded the North Carolina ACS Distinguished Speaker Award.
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Posted by on July 1, 2007 in ChemSpider Chemistry

 

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