Fragment-Based Drug Discovery
From Proteopedia
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= Ligand-Based Drug Design: SAR by NMR = | = Ligand-Based Drug Design: SAR by NMR = | ||
| - | Ligand-based drug design (LBDD) techniques are applied when the structure of the receptor is unknown but when a series of compounds or ligands have been identified that show the biological activity of the interest.<ref name="Pandit D. LIGAND-BASED DRUG DESIGN: I. CONFORMATIONAL STUDIES OF GBR 12909 ANALOGS AS COCAINE ANTAGONISTS; II. 3D-QSAR STUDIES OF SALVINORIN A ANALOGS AS εΑΡΡΑ OPIOID AGONISTS. http://archives.njit.edu/vol01/etd/2000s/2007/njit-etd2007-051/njit-etd2007-051.pdf">Pandit D. LIGAND-BASED DRUG DESIGN: I. CONFORMATIONAL STUDIES OF GBR 12909 ANALOGS AS COCAINE ANTAGONISTS; II. 3D-QSAR STUDIES OF SALVINORIN A ANALOGS AS εΑΡΡΑ OPIOID AGONISTS. http://archives.njit.edu/vol01/etd/2000s/2007/njit-etd2007-051/njit-etd2007-051.pdf</ref> In other words, once it is known how a ligand binds to a protein or any other molecule, new ligands can be designed to bind in a similar manner and get the desired effect. | + | "Ligand-based drug design (LBDD) techniques are applied when the structure of the receptor is unknown but when a series of compounds or ligands have been identified that show the biological activity of the interest."<ref name="Pandit D. LIGAND-BASED DRUG DESIGN: I. CONFORMATIONAL STUDIES OF GBR 12909 ANALOGS AS COCAINE ANTAGONISTS; II. 3D-QSAR STUDIES OF SALVINORIN A ANALOGS AS εΑΡΡΑ OPIOID AGONISTS. http://archives.njit.edu/vol01/etd/2000s/2007/njit-etd2007-051/njit-etd2007-051.pdf">Pandit D. LIGAND-BASED DRUG DESIGN: I. CONFORMATIONAL STUDIES OF GBR 12909 ANALOGS AS COCAINE ANTAGONISTS; II. 3D-QSAR STUDIES OF SALVINORIN A ANALOGS AS εΑΡΡΑ OPIOID AGONISTS. http://archives.njit.edu/vol01/etd/2000s/2007/njit-etd2007-051/njit-etd2007-051.pdf</ref> In other words, once it is known how a ligand binds to a protein or any other molecule, new ligands, and eventually drugs, can be designed to bind in a similar manner and get the desired effect. |
<StructureSection load='1ysi' size='500' side='right' caption=' ' scene='Sandbox_reserved_394/Bcl-xl/1'> | <StructureSection load='1ysi' size='500' side='right' caption=' ' scene='Sandbox_reserved_394/Bcl-xl/1'> | ||
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=== SAR by NMR === | === SAR by NMR === | ||
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| - | One tool used in ligand-based design is structure-activity relationship (SAR) by nuclear magnetic resonance (NMR). This is a process "in which small organic molecules that bind to proximal subsites of a protein are identified, optimized, and linked together to produce high-affinity ligands."<ref name="Shuker S. B., Hajduk P. J., Meadows R. P., Fesik S. W. Discovering High-Affinity Ligands for Proteins: SAR by NMR. Science; Nov 29, 1996; 274, 5292; ProQuest Central pg. 1531.">Shuker S. B., Hajduk P. J., Meadows R. P., Fesik S. W. Discovering High-Affinity Ligands for Proteins: SAR by NMR. Science; Nov 29, 1996; 274, 5292; ProQuest Central pg. 1531.</ref> This | + | One tool used in ligand-based design is structure-activity relationship (SAR) by nuclear magnetic resonance (NMR). This is a process "in which small organic molecules that bind to proximal subsites of a protein are identified, optimized, and linked together to produce high-affinity ligands."<ref name="Shuker S. B., Hajduk P. J., Meadows R. P., Fesik S. W. Discovering High-Affinity Ligands for Proteins: SAR by NMR. Science; Nov 29, 1996; 274, 5292; ProQuest Central pg. 1531.">Shuker S. B., Hajduk P. J., Meadows R. P., Fesik S. W. Discovering High-Affinity Ligands for Proteins: SAR by NMR. Science; Nov 29, 1996; 274, 5292; ProQuest Central pg. 1531.</ref> This process involves analyzing ligands that have some affinity for a protein or other molecule and identifying the structural components of the ligands that are responsible for the binding affinity. |
SAR by NMR has high potential for drug development as it can be used to develop drugs that have very high affinity for specific drug targets. Using this tool also allows drug developers to create new drugs with minimal chemical synthesis, which then decreases the cost and time required to discover and develop new drugs. | SAR by NMR has high potential for drug development as it can be used to develop drugs that have very high affinity for specific drug targets. Using this tool also allows drug developers to create new drugs with minimal chemical synthesis, which then decreases the cost and time required to discover and develop new drugs. | ||
Revision as of 18:28, 24 October 2012
Ligand-Based Drug Design: SAR by NMR
"Ligand-based drug design (LBDD) techniques are applied when the structure of the receptor is unknown but when a series of compounds or ligands have been identified that show the biological activity of the interest."[1] In other words, once it is known how a ligand binds to a protein or any other molecule, new ligands, and eventually drugs, can be designed to bind in a similar manner and get the desired effect.
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References
- ↑ Pandit D. LIGAND-BASED DRUG DESIGN: I. CONFORMATIONAL STUDIES OF GBR 12909 ANALOGS AS COCAINE ANTAGONISTS; II. 3D-QSAR STUDIES OF SALVINORIN A ANALOGS AS εΑΡΡΑ OPIOID AGONISTS. http://archives.njit.edu/vol01/etd/2000s/2007/njit-etd2007-051/njit-etd2007-051.pdf
- ↑ Shuker S. B., Hajduk P. J., Meadows R. P., Fesik S. W. Discovering High-Affinity Ligands for Proteins: SAR by NMR. Science; Nov 29, 1996; 274, 5292; ProQuest Central pg. 1531.
- ↑ Oltersdorf T., Elmore S. W., Shoemaker A. R. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Vol 435|2 June 2005|doi:10.1038/nature03579
