[NMR paper] Identification of differential protein binding affinities in an atropisomeric pharmaceutical compound using non-covalent mass spectrometry, equilibrium dialysis and NMR.
Identification of differential protein binding affinities in an atropisomeric pharmaceutical compound using non-covalent mass spectrometry, equilibrium dialysis and NMR.
Related ArticlesIdentification of differential protein binding affinities in an atropisomeric pharmaceutical compound using non-covalent mass spectrometry, equilibrium dialysis and NMR.
Anal Chem. 2013 May 22;
Authors: Maple HJ, Garlish RA, Whitcombe I, Hold A, Prosser CE, Ford D, Mackenzie H, Crosby J, Porter J, Taylor RJ, Crump MP
Abstract
Atropisomerism of pharmaceutical compounds is a challenging area for drug discovery programs.1 Strategies for dealing with these compounds include raising the energy barrier to atropisomerisation in order to develop the drug as a single isomer,2 or reducing the barrier to rotation and developing a mixture of rapidly interconverting isomers.3 Commonly, however, the atropisomers will be differentiated in terms of their affinity for a given protein target, and it is therefore important to rapidly identify the most active component prior to further compound development. We present equilibrium dialysis and saturation transfer difference-NMR (STD-NMR) as techniques for assessing relative affinities of an atropisomeric mixture against anti-apoptotic protein targets, Bcl-2 and Bcl-xL. These techniques require no prior separation of the mixture of compounds and are therefore rapid and simple approaches. We also explore the use of non-covalent mass spectrometry for determining KD values of individual atropisomers separated from the equilibrium mixture, and compare the results to solution phase measurements. Results from equilibrium dialysis, STD-NMR and non-covalent mass spectrometry are all in excellent agreement, and provide complementary information on differential binding, amplification of the strongest binders and KD values.
PMID: 23697870 [PubMed - as supplied by publisher]
[NMR paper] Native mass spectrometry of photosynthetic pigment-protein complexes.
Native mass spectrometry of photosynthetic pigment-protein complexes.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles Native mass spectrometry of photosynthetic pigment-protein complexes.
FEBS Lett. 2013 Jan 18;
Authors: Zhang H, Cui W, Gross ML, Blankenship RE
Abstract
Native mass spectrometry (MS), or as is sometimes called "native electrospray ionization" allows proteins in their native or near-native states in solution to be introduced into the gas phase and...
nmrlearner
Journal club
0
02-03-2013 10:19 AM
[Question from NMRWiki Q&A forum] Dimer and tetramer equilibrium identification of protein with NMR experiments
Dimer and tetramer equilibrium identification of protein with NMR experiments
Dear nmr wikiers
could you please let me know is their any nmr experment to identification of Dimer and tetramer equilibrium of protein with NMR experiments ?
thanks in advance .
Regards
nmrlearner
News from other NMR forums
0
06-22-2011 03:51 PM
[NMR paper] NMR and mass spectrometry studies of putative interactions of cell cycle proteins pRb
NMR and mass spectrometry studies of putative interactions of cell cycle proteins pRb and CDK6 with cell differentiation proteins MyoD and ID-2.
Related Articles NMR and mass spectrometry studies of putative interactions of cell cycle proteins pRb and CDK6 with cell differentiation proteins MyoD and ID-2.
Biochim Biophys Acta. 2005 Jun 15;1750(1):48-60
Authors: Smialowski P, Singh M, Mikolajka A, Majumdar S, Joy JK, Nalabothula N, Krajewski M, Degenkolbe R, Bernard HU, Holak TA
Cell growth and differentiation require precise coordination of...
nmrlearner
Journal club
0
11-25-2010 08:21 PM
[NMR paper] Mass spectrometry assisted assignment of NMR resonances in 15N labeled proteins.
Mass spectrometry assisted assignment of NMR resonances in 15N labeled proteins.
Related Articles Mass spectrometry assisted assignment of NMR resonances in 15N labeled proteins.
J Am Chem Soc. 2004 Nov 10;126(44):14377-9
Authors: Feng L, Orlando R, Prestegard JH
Application of nuclear magnetic resonance (NMR) methods for the structural characterization to larger and more complex protein systems can be facilitated through the development of new methods for resonance assignment. Here, a novel approach that relies on integration of NMR and mass...
nmrlearner
Journal club
0
11-24-2010 10:03 PM
[NMR paper] Lipid analysis of human HDL and LDL by MALDI-TOF mass spectrometry and (31)P-NMR.
Lipid analysis of human HDL and LDL by MALDI-TOF mass spectrometry and (31)P-NMR.
Related Articles Lipid analysis of human HDL and LDL by MALDI-TOF mass spectrometry and (31)P-NMR.
J Lipid Res. 2001 Sep;42(9):1501-8
Authors: Schiller J, Zschörnig O, Petkovi? M, Müller M, Arnhold J, Arnold K
The analysis of HDL and LDL is important for the further understanding of atherosclerosis because changes of the protein and lipid moieties occur under pathological conditions. Because destruction of lipids leads to the formation of well-defined products...
nmrlearner
Journal club
0
11-19-2010 08:44 PM
[NMR paper] Mass spectrometry--a useful tool for the protein X-ray crystallographer and NMR spect
Mass spectrometry--a useful tool for the protein X-ray crystallographer and NMR spectroscopist.
Related Articles Mass spectrometry--a useful tool for the protein X-ray crystallographer and NMR spectroscopist.
Structure. 1994 Jun 15;2(6):465-7
Authors: Chait BT
nmrlearner
Journal club
0
08-22-2010 03:33 AM
[NMR paper] Mass spectrometry--a useful tool for the protein X-ray crystallographer and NMR spect
Mass spectrometry--a useful tool for the protein X-ray crystallographer and NMR spectroscopist.
Related Articles Mass spectrometry--a useful tool for the protein X-ray crystallographer and NMR spectroscopist.
Structure. 1994 Jun 15;2(6):465-7
Authors: Chait BT
nmrlearner
Journal club
0
08-22-2010 03:33 AM
Tenured Academic Staff - Mass spectrometry, University of Antwerp
I found the following job on spectroscopyNOW.com
Contact Name: Prof. Dr. R. Dommisse
Contact Email: Roger.Dommisse@ua.ac.be
Contact Telephone: +32 3 265 32 29
Employer: University of Antwerp
Background
Identification of differential protein binding affinities in an atropisomeric pharmaceutical compound using non-covalent mass spectrometry, equilibrium dialysis and NMR.
Linear Mode
