scholarly journals Circular dichroism and synchrotron radiation circular dichroism spectroscopy: tools for drug discovery

2003 ◽  
Vol 31 (6) ◽  
pp. 1531-1531 ◽  
Author(s):  
B.A. WALLACE ◽  
ROBERT W. JANES
Keyword(s):  
Circular Dichroism ◽  
Drug Discovery ◽  
Synchrotron Radiation ◽  
Circular Dichroism Spectroscopy ◽  
Title Page ◽  
Online Journal ◽  
Circular Dichroïsm

On the title page of the article (p. 631), the first author's name was shown incorrectly as “Bonnie A. Wallace”; this should have been “B.A. Wallace”. This has been corrected for the online journal.

Synchrotron radiation circular dichroism spectroscopy applied to metmyoglobin and a 4-?-helix bundle carboprotein

Biopolymers ◽  
2005 ◽  
Vol 78 (1) ◽  
pp. 46-52 ◽  
Author(s):  
Peter W. Thulstrup ◽  
Jesper Brask ◽  
Knud J. Jensen ◽  
Erik Larsen
Keyword(s):  
Circular Dichroism ◽  
Synchrotron Radiation ◽  
Circular Dichroism Spectroscopy ◽  
Helix Bundle ◽  
Circular Dichroïsm

Synchrotron radiation circular dichroism (SRCD) spectroscopy: an enhanced method for examining protein conformations and protein interactions

2010 ◽  
Vol 38 (4) ◽  
pp. 861-873 ◽  
Author(s):  
B.A. Wallace ◽  
Robert W. Janes
Keyword(s):  
Circular Dichroism ◽  
Synchrotron Radiation ◽  
Protein Interactions ◽  
Structural Information ◽  
Data Bank ◽  
Cd Spectroscopy ◽  
Circular Dichroism Spectroscopy ◽  
Protein Conformations ◽  
Mutant Proteins ◽  
Circular Dichroïsm

CD (circular dichroism) spectroscopy is a well-established technique in structural biology. SRCD (synchrotron radiation circular dichroism) spectroscopy extends the utility and applications of conventional CD spectroscopy (using laboratory-based instruments) because the high flux of a synchrotron enables collection of data at lower wavelengths (resulting in higher information content), detection of spectra with higher signal-to-noise levels and measurements in the presence of absorbing components (buffers, salts, lipids and detergents). SRCD spectroscopy can provide important static and dynamic structural information on proteins in solution, including secondary structures of intact proteins and their domains, protein stability, the differences between wild-type and mutant proteins, the identification of natively disordered regions in proteins, and the dynamic processes of protein folding and membrane insertion and the kinetics of enzyme reactions. It has also been used to effectively study protein interactions, including protein–protein complex formation involving either induced-fit or rigid-body mechanisms, and protein–lipid complexes. A new web-based bioinformatics resource, the Protein Circular Dichroism Data Bank (PCDDB), has been created which enables archiving, access and analyses of CD and SRCD spectra and supporting metadata, now making this information publicly available. To summarize, the developing method of SRCD spectroscopy has the potential for playing an important role in new types of studies of protein conformations and their complexes.

Circular dichroism and synchrotron radiation circular dichroism spectroscopy: tools for drug discovery

2003 ◽  
Vol 31 (3) ◽  
pp. 631-633 ◽  
Author(s):  
B.A. Wallace ◽  
Robert W. Janes
Keyword(s):  
Circular Dichroism ◽  
Drug Discovery ◽  
Synchrotron Radiation ◽  
High Throughput ◽  
Conformational Changes ◽  
High Throughput Screening ◽  
Cd Spectroscopy ◽  
Drug Binding ◽  
Apoptosis Protein ◽  
Circular Dichroïsm

CD spectroscopy is an established and valuable technique for examining protein structure, dynamics and folding. Because of its ability to sensitively detect conformational changes, it has important potential for drug discovery, enabling screening for ligand and drug binding, and detection of potential candidates for new pharmaceuticals. The binding of the anti-tumour agent Taxol to the anti-apoptosis protein Bcl-2 [Rodi, Janes, Sanganee, Holton, Wallace and Makowski (1999) J. Mol. Biol. 285, 197–204] and the binding of the anti-epileptic drug lamotrigine to voltage-gated sodium channels [Cronin, O'Reilly, Duclohier and Wallace (2003) J. Biol. Chem. 278, 10675–10682] are used as examples to show changes detectable by CD involving secondary structure, and are contrasted with the binding of the agonist carbamylcholine to acetylcholine receptors [Mielke and Wallace (1988) J. Biol. Chem. 263, 8177–8182], an example where binding does not involve a secondary structural change. Synchrotron radiation CD spectroscopy offers significant enhancements with respect to conventional CD spectroscopy, which will enable its usage for high-throughput screening and as a tool in ‘chemical genomics’ or ‘reverse chemical genetics’ strategies for ligand identification. The lower wavelength data available enable more detailed, sensitive and accurate detection, the higher light intensity permits much smaller amounts of both proteins and drug candidates to be used in the screening, and future technological developments in sample handling and detection should enable automated high-throughput screening to be performed.

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