Understanding small-molecule binding to MDM2: insights into structural effects of isoindolinone inhibitors from NMR spectroscopy.
Chem Biol Drug Des. 2011 May;77(5):301-8
Authors: Riedinger C, Noble ME, Wright DJ, Mulks F, Hardcastle IR, Endicott JA, McDonnell JM
The interaction between murine double minute (MDM2) and p53 is a major target in anticancer drug design. Several potent compound series, including the nutlins and spirooxindoles, have previously been established as high-affinity antagonists of MDM2. In this paper, we describe the interaction of isoindolinone inhibitors with MDM2, as characterized by nuclear magnetic resonance spectroscopy. Isoindolinone inhibitors bind specifically to the MDM2 p53 binding site and exploit all sub-pockets used by p53, nutlins and spirooxindoles. Furthermore, isoindolinones bind with low micromolar to high nanomolar affinities, with the best compound approaching the potency of nutlin-3.
[CNS Yahoo group] How to add bond between protein residue and a small molecule in CNS
How to add bond between protein residue and a small molecule in CNS
Dear All, I'm stuck in a step where in i need to connect a bond an amino acid residue and a small molecule in CNS Thank you. Joseph
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08-07-2011 01:35 AM
[Question from NMRWiki Q&A forum] About paragnetic impurities, inorganic salts, bad workups, etc. and their impact on small-molecule NMR spectra
About paragnetic impurities, inorganic salts, bad workups, etc. and their impact on small-molecule NMR spectra
I sometimes face the challenge of explaining to my organic chemists that, even if no impurity signals are visible in their 1H spectrum, other signs (like FID shape, very poor s/n compared to what could be expected with the sample qty, broad peaks, bad resolution...) indicate that clearly, something is wrong with their sample.
Everybody would agree that it's way much easier to convince an invidual based on concrete facts ("look, here we can see solvent/starting material/side...
nmrlearner
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03-31-2011 09:21 PM
Preparation of protein samples for NMR structure, function, and small-molecule screening studies.
Preparation of protein samples for NMR structure, function, and small-molecule screening studies.
Preparation of protein samples for NMR structure, function, and small-molecule screening studies.
Methods Enzymol. 2011;493:21-60
Authors: Acton TB, Xiao R, Anderson S, Aramini J, Buchwald WA, Ciccosanti C, Conover K, Everett J, Hamilton K, Huang YJ, Janjua H, Kornhaber G, Lau J, Lee DY, Liu G, Maglaqui M, Ma L, Mao L, Patel D, Rossi P, Sahdev S, Shastry R, Swapna GV, Tang Y, Tong S, Wang D, Wang H, Zhao L, Montelione GT
In this chapter, we...
nmrlearner
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03-05-2011 01:02 PM
[NMR paper] QSAR-by-NMR: quantitative insights into structural determinants for binding affinity
QSAR-by-NMR: quantitative insights into structural determinants for binding affinity by analysis of 1H/15N chemical shift differences in MMP-3 ligands.
Related Articles QSAR-by-NMR: quantitative insights into structural determinants for binding affinity by analysis of 1H/15N chemical shift differences in MMP-3 ligands.
Bioorg Med Chem Lett. 2005 Apr 1;15(7):1779-83
Authors: Matter H, Schudok M, Elshorst B, Jacobs DM, Saxena K, Kogler H
A novel strategy is applied to obtain quantitative insights on factors influencing biological affinity in...
nmrlearner
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11-25-2010 08:21 PM
[NMR paper] NMR structure of a complex between MDM2 and a small molecule inhibitor.
NMR structure of a complex between MDM2 and a small molecule inhibitor.
Related Articles NMR structure of a complex between MDM2 and a small molecule inhibitor.
J Biomol NMR. 2004 Oct;30(2):163-73
Authors: Fry DC, Emerson SD, Palme S, Vu BT, Liu CM, Podlaski F
MDM2 is a regulator of cell growth processes that acts by binding to the tumor suppressor protein p53 and ultimately restraining its activity. While inactivation of p53 by mutation is commonly observed in human cancers, a substantial percentage of tumors express wild type p53. In many of...
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11-24-2010 10:01 PM
[NMR paper] New structural insights into carbohydrate-protein interactions from NMR spectroscopy.
New structural insights into carbohydrate-protein interactions from NMR spectroscopy.
Related Articles New structural insights into carbohydrate-protein interactions from NMR spectroscopy.
Curr Opin Struct Biol. 2003 Oct;13(5):646-53
Authors: Kogelberg H, Solís D, Jiménez-Barbero J
Recently developed NMR methods have been applied to discover carbohydrate ligands for proteins and to identify their binding epitopes. The structural details of carbohydrate-protein complexes have also been examined by NMR, providing site-specific information on the...
nmrlearner
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11-24-2010 09:16 PM
Novel Small Molecule Inhibitors of MDR Mycobacterium tuberculosis by NMR Fragment Scr
Novel Small Molecule Inhibitors of MDR Mycobacterium tuberculosis by NMR Fragment Screening of Antigen 85C.
Related Articles Novel Small Molecule Inhibitors of MDR Mycobacterium tuberculosis by NMR Fragment Screening of Antigen 85C.
J Med Chem. 2010 Nov 12;
Authors: Scheich C, Puetter V, Schade M
Protein target-based discovery of novel antibiotics has been largely unsuccessful despite rich genome information. Particularly in need are new antibiotics for tuberculosis, which kills 1.6 million people annually and shows a rapid increase in...
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11-16-2010 04:13 PM
Small Molecule NMR Scientist (B.S./ M.S.) at Novartis Ag (Cambridge, MA)
Small Molecule NMR Scientist (B.S./ M.S.) at Novartis Ag (Cambridge, MA)
using the state-of-the-art NMR methodologies. As an NMR scientist within the team, you will be responsible for ... in small molecular NMR with demonstrated success in modern NMR methodologies. Demonstrated skills in data collection...
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Understanding small-molecule binding to MDM2: insights into structural effects of isoindolinone inhibitors from NMR spectroscopy.
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