2qgd
From Proteopedia
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'''Human transthyretin (TTR) complexed with 2-(3,5-Dibromo-4-hydroxyphenyl)benzoxazole''' | '''Human transthyretin (TTR) complexed with 2-(3,5-Dibromo-4-hydroxyphenyl)benzoxazole''' | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Connelly, S.]] | [[Category: Connelly, S.]] | ||
| - | [[Category: | + | [[Category: Amyloidogenesis inhibitor]] |
| - | [[Category: | + | [[Category: Hormone/growth factor complex]] |
| - | [[Category: | + | [[Category: Tetramer]] |
| - | [[Category: | + | [[Category: Transthyretin]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 14:54:40 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 11:54, 4 May 2008
Human transthyretin (TTR) complexed with 2-(3,5-Dibromo-4-hydroxyphenyl)benzoxazole
Overview
To develop potent transthyretin (TTR) amyloidogenesis inhibitors that also display high binding selectivity in blood, it proves useful to systematically optimize each of the three substructural elements that comprise a typical inhibitor: the two aryl rings and the linker joining them. In the first study, described herein, structural modifications to one aryl ring were evaluated by screening a library of 2-arylbenzoxazoles bearing thyroid hormone-like aryl substituents on the 2-aryl ring. Several potent and highly selective amyloidogenesis inhibitors were identified that exhibit minimal thyroid hormone nuclear receptor and COX-1 binding. High resolution crystal structures (1.3-1.5 A) of three inhibitors (2f, 4f, and 4d) in complex with TTR were obtained to characterize their binding orientation. Collectively, the results demonstrate that thyroid hormone-like substitution patterns on one aryl ring lead to potent and highly selective TTR amyloidogenesis inhibitors that lack undesirable thyroid hormone receptor or COX-1 binding.
About this Structure
2QGD is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Biochemical and structural evaluation of highly selective 2-arylbenzoxazole-based transthyretin amyloidogenesis inhibitors., Johnson SM, Connelly S, Wilson IA, Kelly JW, J Med Chem. 2008 Jan 24;51(2):260-70. Epub 2007 Dec 21. PMID:18095641 Page seeded by OCA on Sun May 4 14:54:40 2008
