STD NMR spectroscopy is extensively used to obtain epitope maps of ligands binding to protein receptors, revealing structural details of the interaction, which is key to direct lead optimization efforts in drug discovery. However, it does not give information about the nature of the amino acids surrounding the ligand in the binding pocket. Here we report the development of a novel protocol, Differential Epitope Mapping by STD NMR (DEEP-STD NMR), to identify the type of protein residues contacting the ligand. The protocol produces Differential Epitope Maps by performing (1) differential frequencies STD NMR and/or (2) differential solvent (D2O/H2O) STD NMR experiments. Both approaches provide different complementary information on the binding pocket. We demonstrate that DEEP-STD NMR can be used to readily obtain pharmacophore information on the protein. Furthermore, if the 3D structure of the protein is known, this information also helps orienting the ligand in the binding pocket.
[NMR paper] Q2DSTD NMR deciphers epitope-mapping variability for peptide recognition of integrin ?v?6.
Q2DSTD NMR deciphers epitope-mapping variability for peptide recognition of integrin ?v?6.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.rsc.org-images-entities-char_z_RSClogo.gif http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.ncbi.nlm.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.gif Related Articles Q2DSTD NMR deciphers epitope-mapping variability for peptide recognition of integrin ?v?6.
Org Biomol Chem. 2015 Aug 7;13(29):8001-7
Authors: Sorge JL, Wagstaff JL, Rowe ML, Williamson RA, Howard MJ...
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[NMR paper] Epitope mapping by solution NMR spectroscopy.
Epitope mapping by solution NMR spectroscopy.
Epitope mapping by solution NMR spectroscopy.
J Mol Recognit. 2015 Feb 27;
Authors: Bardelli M, Livoti E, Simonelli L, Pedotti M, Moraes A, Valente AP, Varani L
Abstract
Antibodies play an ever more prominent role in basic research as well as in the biotechnology and pharmaceutical sectors. Characterizing their epitopes, that is, the region that they recognize on their target molecule, is useful for purposes ranging from molecular biology research to vaccine design and intellectual...
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Protein-ligand docking guided by ligand pharmacophore-mapping experiment by NMR.
Protein-ligand docking guided by ligand pharmacophore-mapping experiment by NMR.
Protein-ligand docking guided by ligand pharmacophore-mapping experiment by NMR.
J Mol Graph Model. 2011 Sep 3;
Authors: Fukunishi Y, Mizukoshi Y, Takeuchi K, Shimada I, Takahashi H, Nakamura H
Abstract
We developed a new protein-ligand docking calculation method using experimental NMR data. Recently, we proposed a novel ligand epitope-mapping experiment, which utilizes the difference between the longitudinal relaxation rates of ligand protons with and...
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09-24-2011 04:11 PM
[NMR paper] Selective interface detection: mapping binding site contacts in membrane proteins by
Selective interface detection: mapping binding site contacts in membrane proteins by NMR spectroscopy.
Related Articles Selective interface detection: mapping binding site contacts in membrane proteins by NMR spectroscopy.
J Am Chem Soc. 2005 Apr 27;127(16):5734-5
Authors: Kiihne SR, Creemers AF, de Grip WJ, Bovee-Geurts PH, Lugtenburg J, de Groot HJ
Intermolecular contact surfaces are important regions where specific interactions mediate biological function. We introduce a new magic angle spinning solid state NMR technique, dubbed "selective...
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11-25-2010 08:21 PM
[NMR paper] Epitope mapping of the phosphorylation motif of the HIV-1 protein Vpu bound to the se
Epitope mapping of the phosphorylation motif of the HIV-1 protein Vpu bound to the selective monoclonal antibody using TRNOESY and STD NMR spectroscopy.
Related Articles Epitope mapping of the phosphorylation motif of the HIV-1 protein Vpu bound to the selective monoclonal antibody using TRNOESY and STD NMR spectroscopy.
Biochemistry. 2004 Nov 23;43(46):14555-65
Authors: Gharbi-Benarous J, Bertho G, Evrard-Todeschi N, Coadou G, Megy S, Delaunay T, Benarous R, Girault JP
The conformational preferences of a 22-amino acid peptide...
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[NMR paper] Epitope mapping and competitive binding of HSA drug site II ligands by NMR diffusion
Epitope mapping and competitive binding of HSA drug site II ligands by NMR diffusion measurements.
Related Articles Epitope mapping and competitive binding of HSA drug site II ligands by NMR diffusion measurements.
J Am Chem Soc. 2004 Nov 3;126(43):14258-66
Authors: Lucas LH, Price KE, Larive CK
It is important to characterize drug-albumin binding during drug discovery and lead optimization as strong binding may reduce bioavailability and/or increase the drug's in vivo half-life. Despite knowing about the location of human serum albumin (HSA)...
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[NMR paper] Epitope mapping of ligand-receptor interactions by diffusion NMR.
Epitope mapping of ligand-receptor interactions by diffusion NMR.
Related Articles Epitope mapping of ligand-receptor interactions by diffusion NMR.
J Am Chem Soc. 2002 Aug 28;124(34):9984-5
Authors: Yan J, Kline AD, Mo H, Zartler ER, Shapiro MJ
A novel method based on diffusion NMR for the epitope mapping of ligand binding is presented. The intermolecular NOE builds up during a long diffusion period and creates a deviation from the linearity. The ligand proton nearest the protein generates the strongest NOE from protein during the diffusion...
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[NMR paper] Group epitope mapping by saturation transfer difference NMR to identify segments of a
Group epitope mapping by saturation transfer difference NMR to identify segments of a ligand in direct contact with a protein receptor.
Related Articles Group epitope mapping by saturation transfer difference NMR to identify segments of a ligand in direct contact with a protein receptor.
J Am Chem Soc. 2001 Jun 27;123(25):6108-17
Authors: Mayer M, Meyer B
A protocol based on saturation transfer difference (STD) NMR spectra was developed to characterize the binding interactions at an atom level, termed group epitope mapping (GEM). As an example...
DiffErential EPitope mapping by STD NMR spectroscopy (DEEP-STD NMR) to reveal the nature of protein-ligand contacts
Linear Mode
