Sandbox Reserved 1105: Difference between revisions

4,6-dicarboxylate derivative of dibenzofuran (DDBF) is bounded according two symmetric equivalent modes <ref name="Petrassi">PMID:15869287</ref>. Indeed, DDBF wears a tricyclic ring system, with 2 hydrogen bond donors and 5 hydrogen bond acceptors, allowing to bound the dimer-dimer interface of the TTR cavity <ref name="National Center for Biotechnology Information">[https://pubchem.ncbi.nlm.nih.gov/compound/Dibenzofuran-4_6-dicarboxylic-acid Link text], PubChem Database. CID:3022(accessed on Dec. 26, 2019).</ref><ref name="Klabunde">PMID:10742177</ref>. Thanks to the complementarity of shape and hydrophobicity, DDBF enters nicely the outer portion of HBPs pockets <ref name="Petrassi "/>. Besides, the tricyclic ring system interacts with <scene name='83/832920/Lys15_leu17_and_ala108/1'>Lys15, Leu17 and Ala108</scene> from two adjacent TTR subunits <ref name="Petrassi"/>.  Additionally, carboxylates at the position 4 and 6 of DDBF make electrostatic interactions at the entrance of HBP1 and HBP1' with <scene name='83/832920/Lys15/3'>Lys15</scene> on the ε-NH3+ groups <ref name="Petrassi"/>.  

TTR in complex with dibenzofuran-4,6-dicarboxylic acid keeps the general apo-structure, with water molecules bind to HBP3 and HBP3’ cavities of TTR <ref name="Klabunde">PMID:10742177</ref>. There is not conformational change of <scene name='83/832920/Ser117/1'>Ser117</scene> and <scene name='83/832920/Thr119/1'>Thr119</scene> of TTR, contrary to other inhibitor, unlike most NSAID.