NMR and protein structure in drug design: application to cyclotides and conotoxins.
Eur Biophys J. 2011 Feb 3;
Authors: Daly NL, Rosengren KJ, Troeira Henriques S, Craik DJ
Nuclear magnetic resonance spectroscopy (NMR) is a powerful technique for determining the structures, dynamics and interactions of molecules, and the derived information can be useful in drug design applications. This article gives a brief overview of the role of NMR in drug design and illustrates this role with examples studied in our laboratory in recent years on disulfide-rich peptides, including cyclotides and conotoxins. Cyclotides are head-to-tail cyclized proteins from plants that are exceptionally stable and hence make useful templates for the stabilization of bioactive peptide epitopes as well as potential leads for anti-HIV drugs. Natural cyclotides target cell membranes, so understanding cyclotide-membrane interactions is useful in applying cyclotides in drug design applications. NMR studies of these interactions are described in this article. Conotoxins are disulfide-rich peptides, from the venoms of marine cone snails, which are of pharmaceutical interest because they potently interact with a range of ion channels, transporters and other receptor sites implicated in disease states. Chemically re-engineering conotoxins to give them a cyclic backbone has been used to engender them with improved biopharmaceutical properties, such as are observed in cyclotides.
PMID: 21290122 [PubMed - as supplied by publisher]
Postdoctoral Fellow in structure-based drug design by NMR ...
Postdoctoral Fellow in structure-based drug design by NMR ...
Postdoctoral Fellow in structure-based drug design by NMR, Heidelberg, Germany. View all science jobs and scientific careers from Nature Jobs, the premier ...
www.nature.com/.../241001-Postdoctoral-Fellow-in-structure-...
More...
nmrlearner
Job marketplace
0
01-15-2012 04:04 AM
Application of NMR and Molecular Docking in Structure-Based Drug Discovery.
Application of NMR and Molecular Docking in Structure-Based Drug Discovery.
Application of NMR and Molecular Docking in Structure-Based Drug Discovery.
Top Curr Chem. 2011 Sep 14;
Authors: Stark JL, Powers R
Abstract
Drug discovery is a complex and costly endeavor, where few drugs that reach the clinical testing phase make it to market. High-throughput screening (HTS) is the primary method used by the pharmaceutical industry to identify initial lead compounds. Unfortunately, HTS has a high failure rate and is not particularly efficient at...
nmrlearner
Journal club
0
09-15-2011 08:31 PM
Fluorine-Protein Interactions and (19)F NMR Isotropic Chemical Shifts: An Empirical Correlation with Implications for Drug Design.
Fluorine-Protein Interactions and (19)F NMR Isotropic Chemical Shifts: An Empirical Correlation with Implications for Drug Design.
Related Articles Fluorine-Protein Interactions and (19)F NMR Isotropic Chemical Shifts: An Empirical Correlation with Implications for Drug Design.
ChemMedChem. 2010 Nov 29;
Authors: Dalvit C, Vulpetti A
An empirical correlation between the fluorine isotropic chemical shifts, measured by (19)F NMR spectroscopy, and the type of fluorine-protein interactions observed in crystal structures is presented. The CF, CF(2), and...
nmrlearner
Journal club
0
12-01-2010 04:41 PM
[NMR paper] The application of x-ray, NMR, and molecular modeling in the design of MMP inhibitors
The application of x-ray, NMR, and molecular modeling in the design of MMP inhibitors.
Related Articles The application of x-ray, NMR, and molecular modeling in the design of MMP inhibitors.
Curr Top Med Chem. 2004;4(12):1311-27
Authors: Rush TS, Powers R
The following review discusses the successful application of X-ray, NMR, and molecular modeling in the design of potent and selective inhibitors of matrix metalloproteinases (MMPs) and TNFalpha-converting enzyme (TACE) from Wyeth. The importance of protein and ligand mobility as it impacts...
nmrlearner
Journal club
0
11-24-2010 09:25 PM
[NMR paper] NMR spectroscopy tools for structure-aided drug design.
NMR spectroscopy tools for structure-aided drug design.
Related Articles NMR spectroscopy tools for structure-aided drug design.
Angew Chem Int Ed Engl. 2004 Jan 3;43(3):290-300
Authors: Homans SW
Biomolecular NMR spectroscopy has expanded dramatically in recent years and is now a powerful tool for the study of structure, dynamics, and interactions of biomolecules. Previous limitations with respect to molecular size are no longer a primary barrier, and systems as large as 900 kDa were recently studied. NMR spectroscopy is already...
nmrlearner
Journal club
0
11-24-2010 09:25 PM
[NMR paper] NMR spectroscopy in structure-based drug design.
NMR spectroscopy in structure-based drug design.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles NMR spectroscopy in structure-based drug design.
Curr Opin Biotechnol. 1999 Feb;10(1):42-7
Authors: Roberts GC
NMR methods for the study of motion in proteins continue to improve, and a number of studies of protein-ligand complexes relevant to drug design have been reported over the past year, for example, studies of fatty-acid-binding protein and SH2 and SH3 domains. These...
NMR and protein structure in drug design: application to cyclotides and conotoxins.
Linear Mode
