Ligand screening by exoproteolysis and mass spectrometry in combination with computer modelling

Josep Villanueva; Gregorio Fernández-Ballester; Enrique Querol; Francesc X. Aviles; Luis Serrano

doi:10.1016/S0022-2836(03)00664-8

Ligand screening by exoproteolysis and mass spectrometry in combination with computer modelling

Josep Villanueva, Gregorio Fernández-Ballester, Enrique Querol, Francesc X. Aviles, Luis Serrano

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

12 Citations (Scopus)

Abstract

Here, we present a new approach for protein ligand screening based on the use of limited exoproteolysis coupled to MALDI-TOF mass spectrometry, combined with computational modelling and prediction of binding energies. As a test for this combined approach, we have screened a combinatorial library containing 8000 peptides (organized in 60 peptide samples) based on positional scanning format. This library is attached to a poly-Pro framework, and screened against the Abl-SH3 domain. The results obtained demonstrated the validity of the experimental and theoretical approaches in identifying better ligands and in rationalizing the changes in affinity. Exoproteolysis coupled to MALDI-TOF mass spectrometry could be used to screen complex libraries in a fast and efficient way. © 2003 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	1039-1048
Journal	Journal of Molecular Biology
Volume	330
Issue number	5
DOIs	https://doi.org/10.1016/S0022-2836(03)00664-8
Publication status	Published - 25 Jul 2003

Keywords

Binding constant
Computer design
Ligand screening
Mass spectrometry
SH3 domain

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title = "Ligand screening by exoproteolysis and mass spectrometry in combination with computer modelling",

abstract = "Here, we present a new approach for protein ligand screening based on the use of limited exoproteolysis coupled to MALDI-TOF mass spectrometry, combined with computational modelling and prediction of binding energies. As a test for this combined approach, we have screened a combinatorial library containing 8000 peptides (organized in 60 peptide samples) based on positional scanning format. This library is attached to a poly-Pro framework, and screened against the Abl-SH3 domain. The results obtained demonstrated the validity of the experimental and theoretical approaches in identifying better ligands and in rationalizing the changes in affinity. Exoproteolysis coupled to MALDI-TOF mass spectrometry could be used to screen complex libraries in a fast and efficient way. {\textcopyright} 2003 Elsevier Ltd. All rights reserved.",

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T1 - Ligand screening by exoproteolysis and mass spectrometry in combination with computer modelling

AU - Villanueva, Josep

AU - Fernández-Ballester, Gregorio

AU - Querol, Enrique

AU - Aviles, Francesc X.

AU - Serrano, Luis

PY - 2003/7/25

Y1 - 2003/7/25

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AB - Here, we present a new approach for protein ligand screening based on the use of limited exoproteolysis coupled to MALDI-TOF mass spectrometry, combined with computational modelling and prediction of binding energies. As a test for this combined approach, we have screened a combinatorial library containing 8000 peptides (organized in 60 peptide samples) based on positional scanning format. This library is attached to a poly-Pro framework, and screened against the Abl-SH3 domain. The results obtained demonstrated the validity of the experimental and theoretical approaches in identifying better ligands and in rationalizing the changes in affinity. Exoproteolysis coupled to MALDI-TOF mass spectrometry could be used to screen complex libraries in a fast and efficient way. © 2003 Elsevier Ltd. All rights reserved.

KW - Binding constant

KW - Computer design

KW - Ligand screening

KW - Mass spectrometry

KW - SH3 domain

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DO - 10.1016/S0022-2836(03)00664-8

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