Screening a fragment cocktail library using ultrafiltration

Sayaka Shibata; Zhongsheng Zhang; Konstantin V. Korotkov; Jaclyn Delarosa; Alberto Napuli; Angela M. Kelley; Natasha Mueller; Jennifer Ross; Frank H. Zucker; Frederick S. Buckner; Ethan A. Merritt; Christophe L.M.J. Verlinde; Wesley C. Van Voorhis; Wim G.J. Hol; Erkang Fan

doi:10.1007/s00216-011-5225-7

Screening a fragment cocktail library using ultrafiltration

Sayaka Shibata, Zhongsheng Zhang, Konstantin V. Korotkov, Jaclyn Delarosa, Alberto Napuli, Angela M. Kelley, Natasha Mueller, Jennifer Ross, Frank H. Zucker, Frederick S. Buckner, Ethan A. Merritt, Christophe L.M.J. Verlinde, Wesley C. Van Voorhis, Wim G.J. Hol, Erkang Fan

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

9 Scopus citations

Abstract

Ultrafiltration provides a generic method to discover ligands for protein drug targets with millimolar to micromolar K _d, the typical range of fragment-based drug discovery. This method was tailored to a 96-well format, and cocktails of fragment-sized molecules, with molecular masses between 150 and 300 Da, were screened against medical structural genomics target proteins. The validity of the method was confirmed through competitive binding assays in the presence of ligands known to bind the target proteins.

Original language	English
Pages (from-to)	1589-1595
Number of pages	7
Journal	Analytical and Bioanalytical Chemistry
Volume	401
Issue number	5
DOIs	https://doi.org/10.1007/s00216-011-5225-7
State	Published - Sep 2011

Bibliographical note

Funding Information:
We thank Eric T. Larson for his critical review of the manuscript. This work was supported by National Institutes of Health grants P50GM64655 (SGPP), P01AI067921 (MSGPP), and AI34501.

Keywords

Compound library
Fragment-based drug discovery
Screening
Ultrafiltration

ASJC Scopus subject areas

Analytical Chemistry
Biochemistry

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10.1007/s00216-011-5225-7

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Shibata, S., Zhang, Z., Korotkov, K. V., Delarosa, J., Napuli, A., Kelley, A. M., Mueller, N., Ross, J., Zucker, F. H., Buckner, F. S., Merritt, E. A., Verlinde, C. L. M. J., Van Voorhis, W. C., Hol, W. G. J., & Fan, E. (2011). Screening a fragment cocktail library using ultrafiltration. Analytical and Bioanalytical Chemistry, 401(5), 1589-1595. https://doi.org/10.1007/s00216-011-5225-7

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abstract = "Ultrafiltration provides a generic method to discover ligands for protein drug targets with millimolar to micromolar K d, the typical range of fragment-based drug discovery. This method was tailored to a 96-well format, and cocktails of fragment-sized molecules, with molecular masses between 150 and 300 Da, were screened against medical structural genomics target proteins. The validity of the method was confirmed through competitive binding assays in the presence of ligands known to bind the target proteins.",

keywords = "Compound library, Fragment-based drug discovery, Screening, Ultrafiltration",

author = "Sayaka Shibata and Zhongsheng Zhang and Korotkov, {Konstantin V.} and Jaclyn Delarosa and Alberto Napuli and Kelley, {Angela M.} and Natasha Mueller and Jennifer Ross and Zucker, {Frank H.} and Buckner, {Frederick S.} and Merritt, {Ethan A.} and Verlinde, {Christophe L.M.J.} and {Van Voorhis}, {Wesley C.} and Hol, {Wim G.J.} and Erkang Fan",

note = "Funding Information: We thank Eric T. Larson for his critical review of the manuscript. This work was supported by National Institutes of Health grants P50GM64655 (SGPP), P01AI067921 (MSGPP), and AI34501.",

year = "2011",

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doi = "10.1007/s00216-011-5225-7",

language = "English",

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AU - Shibata, Sayaka

AU - Zhang, Zhongsheng

AU - Korotkov, Konstantin V.

AU - Delarosa, Jaclyn

AU - Napuli, Alberto

AU - Kelley, Angela M.

AU - Mueller, Natasha

AU - Ross, Jennifer

AU - Zucker, Frank H.

AU - Buckner, Frederick S.

AU - Merritt, Ethan A.

AU - Verlinde, Christophe L.M.J.

AU - Van Voorhis, Wesley C.

AU - Hol, Wim G.J.

AU - Fan, Erkang

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PY - 2011/9

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N2 - Ultrafiltration provides a generic method to discover ligands for protein drug targets with millimolar to micromolar K d, the typical range of fragment-based drug discovery. This method was tailored to a 96-well format, and cocktails of fragment-sized molecules, with molecular masses between 150 and 300 Da, were screened against medical structural genomics target proteins. The validity of the method was confirmed through competitive binding assays in the presence of ligands known to bind the target proteins.

AB - Ultrafiltration provides a generic method to discover ligands for protein drug targets with millimolar to micromolar K d, the typical range of fragment-based drug discovery. This method was tailored to a 96-well format, and cocktails of fragment-sized molecules, with molecular masses between 150 and 300 Da, were screened against medical structural genomics target proteins. The validity of the method was confirmed through competitive binding assays in the presence of ligands known to bind the target proteins.

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KW - Screening

KW - Ultrafiltration

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Screening a fragment cocktail library using ultrafiltration

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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