Abstract
The history of fragment-based drug discovery, with an emphasis on crystallographic methods, is sketched, illuminating various contributions, including our own, which preceded the industrial development of the method. Subsequently, the creation of the BMSC fragment cocktails library is described. The BMSC collection currently comprises 68 cocktails of 10 compounds that are shape-wise diverse. The utility of these cocktails for initiating lead discovery in structure-based drug design has been explored by soaking numerous protein crystals obtained by our MSGPP (Medical Structural Genomics of Pathogenic Protozoa) consortium. Details of the fragment selection and cocktail design procedures, as well as examples of the successes obtained are given. The BMSC Fragment Cocktail recipes are available free of charge and are in use in over 20 academic labs.
Keywords: Structural genomics, drug design, malaria, trypanosomiasis, leishmaniasis, history
Current Topics in Medicinal Chemistry
Title: Fragment-Based Cocktail Crystallography by the Medical Structural Genomics of Pathogenic Protozoa Consortium
Volume: 9 Issue: 18
Author(s): Jonathan M. Caruthers, Wim G.J. Hol, Ethan A. Merritt, Frederick S. Buckner, Wesley C. Van Voorhis, Frank Zucker, Natasha Mueller, Angela Kelley, Alberto Napuli, Isolde LeTrong, Eric T. Larson, Christophe L.M.J. Verlinde, Jurgen Bosch, Tracy L. Arakaki, Liren Xiao, Jessica Kim, Jennifer Ross, Wei Deng, Zhihua Sun, Zhongsheng Zhang, Sayaka Shibata and Erkang Fan
Affiliation:
Keywords: Structural genomics, drug design, malaria, trypanosomiasis, leishmaniasis, history
Abstract: The history of fragment-based drug discovery, with an emphasis on crystallographic methods, is sketched, illuminating various contributions, including our own, which preceded the industrial development of the method. Subsequently, the creation of the BMSC fragment cocktails library is described. The BMSC collection currently comprises 68 cocktails of 10 compounds that are shape-wise diverse. The utility of these cocktails for initiating lead discovery in structure-based drug design has been explored by soaking numerous protein crystals obtained by our MSGPP (Medical Structural Genomics of Pathogenic Protozoa) consortium. Details of the fragment selection and cocktail design procedures, as well as examples of the successes obtained are given. The BMSC Fragment Cocktail recipes are available free of charge and are in use in over 20 academic labs.
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Cite this article as:
Caruthers M. Jonathan, Hol G.J. Wim, Merritt A. Ethan, Buckner S. Frederick, Van Voorhis C. Wesley, Zucker Frank, Mueller Natasha, Kelley Angela, Napuli Alberto, LeTrong Isolde, Larson T. Eric, Verlinde L.M.J. Christophe, Bosch Jurgen, Arakaki L. Tracy, Xiao Liren, Kim Jessica, Ross Jennifer, Deng Wei, Sun Zhihua, Zhang Zhongsheng, Shibata Sayaka and Fan Erkang, Fragment-Based Cocktail Crystallography by the Medical Structural Genomics of Pathogenic Protozoa Consortium, Current Topics in Medicinal Chemistry 2009; 9 (18) . https://dx.doi.org/10.2174/156802609790102383
DOI https://dx.doi.org/10.2174/156802609790102383 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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