2cn0
COMPLEX OF RECOMBINANT HUMAN THROMBIN WITH A DESIGNED INHIBITOR
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OverviewOverview
In the completion of our fluorine scan of tricyclic inhibitors to map the, fluorophilicity/fluorophobicity of the thrombin active site, a series of, 11 new ligands featuring alkyl, alkenyl, and fluoroalkyl groups was, prepared to explore fluorine effects on binding into the hydrophobic, proximal (P) pocket, lined by Tyr 60A and Trp 60D, His 57, and Leu 99. The, synthesis of the tricyclic scaffolds was based on the 1,3-dipolar, cycloaddition of azomethine ylides, derived from L-proline and, 4-bromobenzaldehyde, with N-(4-fluorobenzyl)maleimide. Introduction of, alkyl, alkenyl, and partially fluorinated alkyl residues was achieved upon, substitution of a sulfonyl group by mixed Mg/Zn organometallics followed, by oxidation/deoxyfluorination, as well as, oxidation/reduction/deoxyfluorination ... [(full description)]
About this StructureAbout this Structure
2CN0 is a [Protein complex] structure of sequences from [Homo sapiens] with NA, CA, F25 and SIN as [ligands]. Active as [Thrombin], with EC number [3.4.21.5]. Structure known Active Site: AC1. Full crystallographic information is available from [OCA].
ReferenceReference
Mapping the fluorophilicity of a hydrophobic pocket: synthesis and biological evaluation of tricyclic thrombin inhibitors directing fluorinated alkyl groups into the p pocket., Hoffmann-Roder A, Schweizer E, Egger J, Seiler P, Obst-Sander U, Wagner B, Kansy M, Banner DW, Diederich F, ChemMedChem. 2006 Nov;1(11):1205-15. PMID:17001711
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