Related ArticlesRanking high affinity ligands of low solubility by NMR spectroscopy.
ACS Med Chem Lett. 2011 Jun 9;2(6):485-7
Authors: Landrieu I, Hanoulle X, Fritzinger B, Horvath D, Wieruszeski JM, Lippens G
Abstract
Cyclosporine A (CsA) and its chemical analogues EthVal4Cs, MeVal4Cs, and Me(d-Ala)3EthVal4Cs (Alisporivir) all interact with cyclophilin A (CypA). The latter Alisporivir is a nonimmunosuppressive CsA derivative that has potent anti-HCV properties in clinical trials. We show here that NMR spectroscopy can be used to rank this series of related pharmacological molecules despite their high affinity for the target protein and low solubility in water. The novel method is based on the possibility to detect distinct NMR signals from the different protein complexes in a mixture. The method has enabled us to distinguish subtle effects of discrete chemical modifications of the parent molecule on the affinity of the ligands for the target protein.
[NMR images] ... PROTEIN solubility determined with the OptiSol protein solubility
http://1.bp.blogspot.com/-7csMp0V8hEo/UXsrKtXoTPI/AAAAAAAAAGU/RIaxBdCKiTA/s640/increasing_solubility_fiv_matrix_protein_NMR_optisol.JPG
31/05/2014 1:57:49 PM GMT
... PROTEIN solubility determined with the OptiSol protein solubility
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05-31-2014 01:57 PM
[NMR paper] NMR screening of new carbocyanine dyes as ligands for affinity chromatography.
NMR screening of new carbocyanine dyes as ligands for affinity chromatography.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--media.wiley.com-assets-2250-98-WileyOnlineLibrary-Button_120x27px_FullText.gif Related Articles NMR screening of new carbocyanine dyes as ligands for affinity chromatography.
J Mol Recognit. 2014 Apr;27(4):197-204
Authors: Cruz C, Boto RE, Drzazga AK, Almeida P, Queiroz JA
Abstract
Four new carbocyanines containing symmetric and asymmetric heterocyclic moieties and N-carboxyalkyl groups have...
nmrlearner
Journal club
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03-05-2014 11:57 PM
Overcoming the solubility limit with solubility-enhancement tags: successful applications in biomolecular NMR studies
Overcoming the solubility limit with solubility-enhancement tags: successful applications in biomolecular NMR studies
Abstract Although the rapid progress of NMR technology has significantly expanded the range of NMR-trackable systems, preparation of NMR-suitable samples that are highly soluble and stable remains a bottleneck for studies of many biological systems. The application of solubility-enhancement tags (SETs) has been highly effective in overcoming solubility and sample stability issues and has enabled structural studies of important biological systems previously deemed...
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01-09-2011 12:46 PM
[NMR paper] Competition STD NMR for the detection of high-affinity ligands and NMR-based screenin
Competition STD NMR for the detection of high-affinity ligands and NMR-based screening.
Related Articles Competition STD NMR for the detection of high-affinity ligands and NMR-based screening.
Magn Reson Chem. 2004 Jun;42(6):485-9
Authors: Wang YS, Liu D, Wyss DF
The reported competition STD NMR method combines saturation transfer difference (STD) NMR with competition binding experiments to allow the detection of high-affinity ligands that undergo slow chemical exchange on the NMR time-scale. With this technique, the presence of a competing...
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11-24-2010 09:51 PM
[NMR paper] NMR probing of protein-protein interactions using reporter ligands and affinity tags.
NMR probing of protein-protein interactions using reporter ligands and affinity tags.
Related Articles NMR probing of protein-protein interactions using reporter ligands and affinity tags.
J Am Chem Soc. 2004 Feb 18;126(6):1636-7
Authors: Ludwiczek ML, Baminger B, Konrat R
A novel method is proposed for the detection and quantification of protein-protein interactions in solution. In this approach, one protein binding partner is tagged with a ligand binding domain, and protein-protein interaction is monitored via changes in the NMR relaxation...
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11-24-2010 09:25 PM
[NMR paper] Solution NMR structure of S100B bound to the high-affinity target peptide TRTK-12.
Solution NMR structure of S100B bound to the high-affinity target peptide TRTK-12.
Related Articles Solution NMR structure of S100B bound to the high-affinity target peptide TRTK-12.
J Mol Biol. 2002 Dec 13;324(5):1003-14
Authors: Inman KG, Yang R, Rustandi RR, Miller KE, Baldisseri DM, Weber DJ
The solution NMR structure is reported for Ca(2+)-loaded S100B bound to a 12-residue peptide, TRTK-12, from the actin capping protein CapZ (alpha1 or alpha2 subunit, residues 265-276: TRTKIDWNKILS). This peptide was discovered by Dimlich and co-workers...
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11-24-2010 08:58 PM
[NMR paper] Discovering high-affinity ligands for proteins: SAR by NMR.
Discovering high-affinity ligands for proteins: SAR by NMR.
Related Articles Discovering high-affinity ligands for proteins: SAR by NMR.
Science. 1996 Nov 29;274(5292):1531-4
Authors: Shuker SB, Hajduk PJ, Meadows RP, Fesik SW
A nuclear magnetic resonance (NMR)-based method is described in which small organic molecules that bind to proximal subsites of a protein are identified, optimized, and linked together to produce high-affinity ligands. The approach is called "SAR by NMR" because structure-activity relationships (SAR) are obtained from...
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08-22-2010 02:20 PM
[NMR paper] Conformational characteristics of high affinity Sp1 binding enhancer elements of HIV-
Conformational characteristics of high affinity Sp1 binding enhancer elements of HIV-LTR by high resolution 2D-NMR.
Related Articles Conformational characteristics of high affinity Sp1 binding enhancer elements of HIV-LTR by high resolution 2D-NMR.
J Biomol Struct Dyn. 1995 Dec;13(3):553-64
Authors: Singh MP, Pon RT, Lown JW
The understanding of early events in the expression of genes has vastly improved in recent years with the identification of a variety of gene- and sequence-specific DNA binding transcription factors. One such protein, Sp1,...
Ranking high affinity ligands of low solubility by NMR spectroscopy.
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