4mi3: Difference between revisions
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4mi3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mi3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mi3 RCSB], [http://www.ebi.ac.uk/pdbsum/4mi3 PDBsum]</span></td></tr> | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4mi3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mi3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mi3 RCSB], [http://www.ebi.ac.uk/pdbsum/4mi3 PDBsum]</span></td></tr> | ||
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== Publication Abstract from PubMed == | |||
Glycogen phosphorylase (GP) is a validated target for the development of new type 2 diabetes treatments. Exploiting the Zinc docking database, we report the in silico screening of 1888 N-acyl-beta-d-glucopyranosylamines putative GP inhibitors differing only in their R groups. CombiGlide and GOLD docking programs with different scoring functions were employed with the best performing methods combined in a 'consensus scoring' approach to ranking of ligand binding affinities for the active site. Six selected candidates from the screening were then synthesized and their inhibitory potency was assessed both in vitro and ex vivo. Their inhibition constants' values, in vitro, ranged from 5 to 377muM while two of them were effective at causing inactivation of GP in rat hepatocytes at low muM concentrations. The crystal structures of GP in complex with the inhibitors were defined and provided the structural basis for their inhibitory potency and data for further structure based design of more potent inhibitors. | |||
Structure based inhibitor design targeting glycogen phosphorylase b. Virtual screening, synthesis, biochemical and biological assessment of novel N-acyl-beta-d-glucopyranosylamines.,Parmenopoulou V, Kantsadi AL, Tsirkone VG, Chatzileontiadou DS, Manta S, Zographos SE, Molfeta C, Archontis G, Agius L, Hayes JM, Leonidas DD, Komiotis D Bioorg Med Chem. 2014 Sep 1;22(17):4810-25. doi: 10.1016/j.bmc.2014.06.058. Epub , 2014 Jul 16. PMID:25092521<ref>PMID:25092521</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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== References == | |||
<references/> | |||
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</StructureSection> | </StructureSection> | ||
Revision as of 10:06, 10 September 2014
Crystal structure of Gpb in complex with SUGAR (N-{(2R)-2-METHYL-3-[4-(PROPAN-2-YL)PHENYL]PROPANOYL}-BETA-D-GLUCOPYRANOSYLAMINE) (S21)Crystal structure of Gpb in complex with SUGAR (N-{(2R)-2-METHYL-3-[4-(PROPAN-2-YL)PHENYL]PROPANOYL}-BETA-D-GLUCOPYRANOSYLAMINE) (S21)
Structural highlights
Publication Abstract from PubMedGlycogen phosphorylase (GP) is a validated target for the development of new type 2 diabetes treatments. Exploiting the Zinc docking database, we report the in silico screening of 1888 N-acyl-beta-d-glucopyranosylamines putative GP inhibitors differing only in their R groups. CombiGlide and GOLD docking programs with different scoring functions were employed with the best performing methods combined in a 'consensus scoring' approach to ranking of ligand binding affinities for the active site. Six selected candidates from the screening were then synthesized and their inhibitory potency was assessed both in vitro and ex vivo. Their inhibition constants' values, in vitro, ranged from 5 to 377muM while two of them were effective at causing inactivation of GP in rat hepatocytes at low muM concentrations. The crystal structures of GP in complex with the inhibitors were defined and provided the structural basis for their inhibitory potency and data for further structure based design of more potent inhibitors. Structure based inhibitor design targeting glycogen phosphorylase b. Virtual screening, synthesis, biochemical and biological assessment of novel N-acyl-beta-d-glucopyranosylamines.,Parmenopoulou V, Kantsadi AL, Tsirkone VG, Chatzileontiadou DS, Manta S, Zographos SE, Molfeta C, Archontis G, Agius L, Hayes JM, Leonidas DD, Komiotis D Bioorg Med Chem. 2014 Sep 1;22(17):4810-25. doi: 10.1016/j.bmc.2014.06.058. Epub , 2014 Jul 16. PMID:25092521[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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