Fragment-based cocktail crystallography by the medical structural genomics of pathogenic protozoa consortium

Christophe L M J Verlinde; Erkang Fan; Sayaka Shibata; Zhongsheng Zhang; Zhihua Sun; Wei Deng; Jennifer Ross; Jessica Kim; Liren Xiao; Tracy L. Arakaki; Jürgen Bosch; Jonathan M. Caruthers; Eric T. Larson; Isolde LeTrong; Alberto Napuli; Angela Kelley; Natasha Mueller; Frank Zucker; Wesley C. Van Voorhis; Frederick S. Buckner; Ethan A. Merritt; Wim G J Hol

doi:10.2174/156802609790102383

Fragment-based cocktail crystallography by the medical structural genomics of pathogenic protozoa consortium

Christophe L M J Verlinde, Erkang Fan, Sayaka Shibata, Zhongsheng Zhang, Zhihua Sun, Wei Deng, Jennifer Ross, Jessica Kim, Liren Xiao, Tracy L. Arakaki, Jürgen Bosch, Jonathan M. Caruthers, Eric T. Larson, Isolde LeTrong, Alberto Napuli, Angela Kelley, Natasha Mueller, Frank Zucker, Wesley C. Van Voorhis, Frederick S. BucknerEthan A. Merritt, Wim G J Hol

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1678-1687
Number of pages	10
Journal	Current Topics in Medicinal Chemistry
Volume	9
Issue number	18
DOIs	https://doi.org/10.2174/156802609790102383
State	Published - 2009
Externally published	Yes

Keywords

Drug design
History
Leishmaniasis
Malaria
Structural genomics
Trypanosomiasis

ASJC Scopus subject areas

Drug Discovery
General Medicine

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10.2174/156802609790102383

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Verlinde, C. L. M. J., Fan, E., Shibata, S., Zhang, Z., Sun, Z., Deng, W., Ross, J., Kim, J., Xiao, L., Arakaki, T. L., Bosch, J., Caruthers, J. M., Larson, E. T., LeTrong, I., Napuli, A., Kelley, A., Mueller, N., Zucker, F., Van Voorhis, W. C., ... Hol, W. G. J. (2009). Fragment-based cocktail crystallography by the medical structural genomics of pathogenic protozoa consortium. Current Topics in Medicinal Chemistry, 9(18), 1678-1687. https://doi.org/10.2174/156802609790102383

Verlinde, CLMJ, Fan, E, Shibata, S, Zhang, Z, Sun, Z, Deng, W, Ross, J, Kim, J, Xiao, L, Arakaki, TL, Bosch, J, Caruthers, JM, Larson, ET, LeTrong, I, Napuli, A, Kelley, A, Mueller, N, Zucker, F, Van Voorhis, WC, Buckner, FS, Merritt, EA & Hol, WGJ 2009, 'Fragment-based cocktail crystallography by the medical structural genomics of pathogenic protozoa consortium', Current Topics in Medicinal Chemistry, vol. 9, no. 18, pp. 1678-1687. https://doi.org/10.2174/156802609790102383

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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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author = "Verlinde, {Christophe L M J} and Erkang Fan and Sayaka Shibata and Zhongsheng Zhang and Zhihua Sun and Wei Deng and Jennifer Ross and Jessica Kim and Liren Xiao and Arakaki, {Tracy L.} and J{\"u}rgen Bosch and Caruthers, {Jonathan M.} and Larson, {Eric T.} and Isolde LeTrong and Alberto Napuli and Angela Kelley and Natasha Mueller and Frank Zucker and {Van Voorhis}, {Wesley C.} and Buckner, {Frederick S.} and Merritt, {Ethan A.} and Hol, {Wim G J}",

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doi = "10.2174/156802609790102383",

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AU - Larson, Eric T.

AU - LeTrong, Isolde

AU - Napuli, Alberto

AU - Kelley, Angela

AU - Mueller, Natasha

AU - Zucker, Frank

AU - Van Voorhis, Wesley C.

AU - Buckner, Frederick S.

AU - Merritt, Ethan A.

AU - Hol, Wim G J

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Fragment-based cocktail crystallography by the medical structural genomics of pathogenic protozoa consortium

Abstract

Keywords

ASJC Scopus subject areas

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