Rapid optimisation of fragments and hits to lead compounds from screening of crude reaction mixtures

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Rapid optimisation of fragments and hits to lead compounds from screening of crude reaction mixtures. / Baker, Lisa M.; Aimon, Anthony; Murray, James B.; Surgenor, Allan E.; Matassova, Natalia; Roughley, Stephen D.; Collins, Patrick M.; Krojer, Tobias; von Delft, Frank; Hubbard, Roderick E.

In: Communications Chemistry, Vol. 3, No. 1, 122, 01.12.2020.

Research output: Contribution to journalArticlepeer-review

Harvard

Baker, LM, Aimon, A, Murray, JB, Surgenor, AE, Matassova, N, Roughley, SD, Collins, PM, Krojer, T, von Delft, F & Hubbard, RE 2020, 'Rapid optimisation of fragments and hits to lead compounds from screening of crude reaction mixtures', Communications Chemistry, vol. 3, no. 1, 122. https://doi.org/10.1038/s42004-020-00367-0

APA

Baker, L. M., Aimon, A., Murray, J. B., Surgenor, A. E., Matassova, N., Roughley, S. D., Collins, P. M., Krojer, T., von Delft, F., & Hubbard, R. E. (2020). Rapid optimisation of fragments and hits to lead compounds from screening of crude reaction mixtures. Communications Chemistry, 3(1), [122]. https://doi.org/10.1038/s42004-020-00367-0

Vancouver

Baker LM, Aimon A, Murray JB, Surgenor AE, Matassova N, Roughley SD et al. Rapid optimisation of fragments and hits to lead compounds from screening of crude reaction mixtures. Communications Chemistry. 2020 Dec 1;3(1). 122. https://doi.org/10.1038/s42004-020-00367-0

Author

Baker, Lisa M. ; Aimon, Anthony ; Murray, James B. ; Surgenor, Allan E. ; Matassova, Natalia ; Roughley, Stephen D. ; Collins, Patrick M. ; Krojer, Tobias ; von Delft, Frank ; Hubbard, Roderick E. / Rapid optimisation of fragments and hits to lead compounds from screening of crude reaction mixtures. In: Communications Chemistry. 2020 ; Vol. 3, No. 1.

Bibtex - Download

@article{adb6d339c4df469198c9de5adad5bba8,
title = "Rapid optimisation of fragments and hits to lead compounds from screening of crude reaction mixtures",
abstract = "Fragment based methods are now widely used to identify starting points in drug discovery and generation of tools for chemical biology. A significant challenge is optimization of these weak binding fragments to hit and lead compounds. We have developed an approach where individual reaction mixtures of analogues of hits can be evaluated without purification of the product. Here, we describe experiments to optimise the processes and then assess such mixtures in the high throughput crystal structure determination facility, XChem. Diffraction data for crystals of the proteins Hsp90 and PDHK2 soaked individually with 83 crude reaction mixtures are analysed manually or with the automated XChem procedures. The results of structural analysis are compared with binding measurements from other biophysical techniques. This approach can transform early hit to lead optimisation and the lessons learnt from this study provide a protocol that can be used by the community.",
author = "Baker, {Lisa M.} and Anthony Aimon and Murray, {James B.} and Surgenor, {Allan E.} and Natalia Matassova and Roughley, {Stephen D.} and Collins, {Patrick M.} and Tobias Krojer and {von Delft}, Frank and Hubbard, {Roderick E.}",
note = "{\textcopyright} The Author(s) 2020",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s42004-020-00367-0",
language = "English",
volume = "3",
journal = "Communications Chemistry",
issn = "2399-3669",
number = "1",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Rapid optimisation of fragments and hits to lead compounds from screening of crude reaction mixtures

AU - Baker, Lisa M.

AU - Aimon, Anthony

AU - Murray, James B.

AU - Surgenor, Allan E.

AU - Matassova, Natalia

AU - Roughley, Stephen D.

AU - Collins, Patrick M.

AU - Krojer, Tobias

AU - von Delft, Frank

AU - Hubbard, Roderick E.

N1 - © The Author(s) 2020

PY - 2020/12/1

Y1 - 2020/12/1

N2 - Fragment based methods are now widely used to identify starting points in drug discovery and generation of tools for chemical biology. A significant challenge is optimization of these weak binding fragments to hit and lead compounds. We have developed an approach where individual reaction mixtures of analogues of hits can be evaluated without purification of the product. Here, we describe experiments to optimise the processes and then assess such mixtures in the high throughput crystal structure determination facility, XChem. Diffraction data for crystals of the proteins Hsp90 and PDHK2 soaked individually with 83 crude reaction mixtures are analysed manually or with the automated XChem procedures. The results of structural analysis are compared with binding measurements from other biophysical techniques. This approach can transform early hit to lead optimisation and the lessons learnt from this study provide a protocol that can be used by the community.

AB - Fragment based methods are now widely used to identify starting points in drug discovery and generation of tools for chemical biology. A significant challenge is optimization of these weak binding fragments to hit and lead compounds. We have developed an approach where individual reaction mixtures of analogues of hits can be evaluated without purification of the product. Here, we describe experiments to optimise the processes and then assess such mixtures in the high throughput crystal structure determination facility, XChem. Diffraction data for crystals of the proteins Hsp90 and PDHK2 soaked individually with 83 crude reaction mixtures are analysed manually or with the automated XChem procedures. The results of structural analysis are compared with binding measurements from other biophysical techniques. This approach can transform early hit to lead optimisation and the lessons learnt from this study provide a protocol that can be used by the community.

UR - http://www.scopus.com/inward/record.url?scp=85090139698&partnerID=8YFLogxK

U2 - 10.1038/s42004-020-00367-0

DO - 10.1038/s42004-020-00367-0

M3 - Article

AN - SCOPUS:85090139698

VL - 3

JO - Communications Chemistry

JF - Communications Chemistry

SN - 2399-3669

IS - 1

M1 - 122

ER -