Related ArticlesEpitope Mapping by NMR of a Novel Anti-A? Antibody (STAB-MAb).
Sci Rep. 2019 08 22;9(1):12241
Authors: Posado-Fernández A, Afonso CF, Dória G, Flores O, Cabrita EJ
Abstract
Alzheimer´s Disease (AD) is one of the most common neurodegenerative disorders worldwide. Excess of ?-amyloid (A?), a peptide with a high propensity to misfold and self-aggregate, is believed to be the major contributor to the observed neuronal degeneration and cognitive decline in AD. Here, we characterize the epitope of a novel anti-A? monoclonal antibody, the STAB-MAb, which has previously demonstrated picomolar affinities for both monomers (KD = 80 pM) and fibrils (KD = 130 pM) of A?(1-42) and has shown therapeutic efficacy in preclinical mouse models of AD. Our findings reveal a widespread epitope that embraces several key A? residues that have been previously described as important in the A? fibrillation process. Of note, STAB-MAb exhibits a stronger affinity for the N-terminus of A? and stabilizes an ?-helix conformation in the central to N-terminal region of the peptide, in addition to disrupting a characteristic salt-bridge of a hairpin structure present in fibrils. The NMR derived epitope supports the observed results from ThT-monitored fluorescence and electron microscopy experiments, in which STAB-MAb was shown to inhibit the formation of aggregates and promote disruption of pre-formed fibrils. In combination with the published in vitro and in vivo assays, our study highlights STAB-MAb as a rare and versatile antibody with analytical, diagnostic and therapeutic efficacy.
[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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03-03-2015 08:34 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 gibberellin to the anti-gibberellin A(4) monoclonal antibody by sa
Epitope mapping of gibberellin to the anti-gibberellin A(4) monoclonal antibody by saturation transfer difference NMR spectroscopy.
Related Articles Epitope mapping of gibberellin to the anti-gibberellin A(4) monoclonal antibody by saturation transfer difference NMR spectroscopy.
Biochem Biophys Res Commun. 2003 Aug 1;307(3):498-502
Authors: Murata T, Hemmi H, Nakajima M, Yoshida M, Yamaguchi I
Saturation transfer difference (STD) NMR spectroscopy is a promising tool for rapid screening, identifying ligands that interact with a target protein,...
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11-24-2010 09:16 PM
[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...
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[NMR paper] NMR structure of an anti-gp120 antibody complex with a V3 peptide reveals a surface i
NMR structure of an anti-gp120 antibody complex with a V3 peptide reveals a surface important for co-receptor binding.
Related Articles NMR structure of an anti-gp120 antibody complex with a V3 peptide reveals a surface important for co-receptor binding.
Structure. 2000 Apr 15;8(4):385-95
Authors: Tugarinov V, Zvi A, Levy R, Hayek Y, Matsushita S, Anglister J
BACKGROUND: The protein 0.5beta is a potent strain-specific human immunodeficiency virus type 1 (HIV-1) neutralizing antibody raised against the entire envelope glycoprotein (gp120) of...
Epitope Mapping by NMR of a Novel Anti-A? Antibody (STAB-MAb).
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