Bruce G. Szczepankiewicz
University of California, Berkeley
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Featured researches published by Bruce G. Szczepankiewicz.
Nature Communications | 2015
Han Dai; April Case; Thomas V. Riera; Thomas Considine; Jessica E. Lee; Yoshitomo Hamuro; Huizhen Zhao; Yong Jiang; Sharon Sweitzer; Beth Pietrak; Benjamin J. Schwartz; Charles A. Blum; Jeremy S. Disch; Richard Caldwell; Bruce G. Szczepankiewicz; Christopher Oalmann; Pui Yee Ng; Brian H. White; Rebecca L. Casaubon; Radha Narayan; Karsten Koppetsch; Francis Bourbonais; Bo Wu; Junfeng Wang; Dongming Qian; Fan Jiang; Cheney Mao; Minghui Wang; Erding Hu; Joseph Wu
SIRT1, the founding member of the mammalian family of seven NAD+-dependent sirtuins, is composed of 747 amino acids forming a catalytic domain and extended N- and C-terminal regions. We report the design and characterization of an engineered human SIRT1 construct (mini-hSIRT1) containing the minimal structural elements required for lysine deacetylation and catalytic activation by small molecule sirtuin-activating compounds (STACs). Using this construct, we solved the crystal structure of a mini-hSIRT1-STAC complex, which revealed the STAC-binding site within the N-terminal domain of hSIRT1. Together with hydrogen-deuterium exchange mass spectrometry (HDX-MS) and site-directed mutagenesis using full-length hSIRT1, these data establish a specific STAC-binding site and identify key intermolecular interactions with hSIRT1. The determination of the interface governing the binding of STACs with human SIRT1 facilitates greater understanding of STAC activation of this enzyme, which holds significant promise as a therapeutic target for multiple human diseases.
Journal of Organic Chemistry | 2012
Bruce G. Szczepankiewicz; Han Dai; Karsten Koppetsch; Dongming Qian; Fan Jiang; Cheney Mao; Robert B. Perni
Carba-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.
Tetrahedron | 1997
Bruce G. Szczepankiewicz; Clayton H. Heathcock
Abstract A method is described for the use of the Fischer indole synthesis to prepare 7-hydroxy-indoles in good yield. The method involves the construction of a 4-aminobenzoxazine and removal of the N-O tether after the indole has been formed.
Journal of Organic Chemistry | 1994
Bruce G. Szczepankiewicz; Clayton H. Heathcock
Organic Process Research & Development | 2014
Toby Broom; Mark Jason Hughes; Bruce G. Szczepankiewicz; Karl W. Ace; Ben Hagger; Gary Lacking; Ranjit Chima; Graeme Marchbank; Gareth Alford; Paul Evans; Christopher Cunningham; John C. Roberts; Robert B. Perni; Malcolm B. Berry; Andrew Rutter; Simon A. Watson
Archive | 2008
Christopher Oalmann; Robert B. Perni; Jeremy S. Disch; Bruce G. Szczepankiewicz; Giovanna Gualtieri; Rebecca L. Casaubon; Karsten Koppetsch
Journal of Organic Chemistry | 2011
Bruce G. Szczepankiewicz; Karsten Koppetsch; Robert B. Perni
Archive | 2015
Bruce G. Szczepankiewicz; Karsten Koppetsch; Robert B. Perni
Archive | 2012
Karsten Koppetsch; Bruce G. Szczepankiewicz; Robert B. Perni
Archive | 2011
Han Dai; Thomas V. Riera; Ross L. Stein; Bruce G. Szczepankiewicz