6 research outputs found
Synthesis of Carba-NAD and the Structures of Its Ternary Complexes with SIRT3 and SIRT5
No full textCarba-NAD is a synthetic compound identical to NAD except
for one
substitution, where an oxygen atom adjacent to the anomeric linkage
bearing nicotinamide is replaced with a methylene group. Because it
is inert in nicotinamide displacement reactions, carba-NAD is an unreactive
substrate analogue for NAD-consuming enzymes. SIRT3 and SIRT5 are
NAD-consuming enzymes that are potential therapeutic targets for the
treatment of metabolic diseases and cancers. We report an improved
carba-NAD synthesis, including a pyrophosphate coupling method that
proceeds in approximately 60% yield. We also disclose the X-ray crystal
structures of the ternary complexes of SIRT3 and SIRT5 bound to a
peptide substrate and carba-NAD. These X-ray crystal structures provide
critical snapshots of the mechanism by which human sirtuins function
as protein deacylation catalysts
Pyrrolidine-3-carboxylic Acids as Endothelin Antagonists. 4. Side Chain Conformational Restriction Leads to ET B
No full textDiscovery of a Potent, Selective Protein Tyrosine Phosphatase 1B Inhibitor Using a Linked-Fragment Strategy
No full textDiscovery and Structure−Activity Relationship of Oxalylarylaminobenzoic Acids as Inhibitors of Protein Tyrosine Phosphatase 1B
No full text
