James C. Powers
Georgia Institute of Technology
Molecular biologyEnzymeProteasesGranzymeChemistryPancreatic elastaseSerineProteaseEnzyme inhibitorCathepsin GSerine proteaseChymotrypsinPeptideIsocoumarinTrypsinElastaseActive siteBiochemistryStereochemistryBiology
Publications 169
#1Christian S. Lentz (Stanford University)H-Index: 10
#2Alvaro A. OrdonezH-Index: 18
Last. Matthew Bogyo (Stanford University)H-Index: 88
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Although serine proteases are important mediators of Mycobacterium tuberculosis (Mtb) virulence, there are currently no tools to selectively block or visualize members of this family of enzymes. Selective reporter substrates or activity-based probes (ABPs) could provide a means to monitor infection and response to therapy using imaging methods. Here, we use a combination of substrate selectivity profiling and focused screening to identify optimized reporter substrates and ABPs for the Mtb “Hydro...
26 CitationsSource
37 CitationsSource
Human polymorphonuclear leukocyte elastase is the enzyme primarily responsible for the destruction of lung tissue observed in pulmonary emphysema. A number of potent reversible and irreversible inhibitors have been developed for human leukocyte elastase. Several of these inhibitors have been shown to be effective at preventing emphysema in animal models of the disease. There are excellent prospects for the development of a synthetic elastase inhibitor for use in treatment of human disease.
19 CitationsSource
The capacity of the synthetic elastase inhibitor, succinyl alanyl alanyl prolyl valine chloromethyl ketone (CMK), to moderate elastase-induced emphysema in hamsters was examined using morphometric and physiologic measurements. When 0.5 mg of CMK in saline was injected intratracheally 1 h before the intratracheal injection of 0.1 mg of porcine pancreatic elastase, the hamsters did not develop emphysema. When CMK was injected intratracheally 1 h after elastase, the severity of emphysema was reduce...
18 CitationsSource
#1Matthew A. Child (Stanford University)H-Index: 12
#2Carolyn I. Hall (Stanford University)H-Index: 2
Last. Matthew BogyoH-Index: 88
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A small-molecule enhancer of Toxoplasma gondii invasion inhibits a previously uncharacterized parasite palmitoyl thioesterase, TgPPT1.
47 CitationsSource
#1Sarina Gloeckl (QUT: Queensland University of Technology)H-Index: 4
#2Vanissa A. Ong (QUT: Queensland University of Technology)H-Index: 6
Last. Wilhelmina M. Huston (QUT: Queensland University of Technology)H-Index: 21
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The mechanistic details of the pathogenesis of Chlamydia, an obligate intracellular pathogen of global importance, have eluded scientists due to the scarcity of traditional molecular genetic tools to investigate this organism. Here we report a chemical biology strategy that has uncovered the first essential protease for this organism. Identification and application of a unique CtHtrA inhibitor (JO146) to cultures of Chlamydia resulted in a complete loss of viable elementary body formation. JO146...
39 CitationsSource
#1Elizabeth L. Ponder (Stanford University)H-Index: 8
#2Victoria E. Albrow (Stanford University)H-Index: 13
Last. Matthew Bogyo (Stanford University)H-Index: 88
view all 14 authors...
Summary Small ubiquitin-related modifier (SUMO) is implicated in the regulation of numerous biological processes including transcription, protein localization, and cell cycle control. Protein modification by SUMO is found in Plasmodium falciparum ; however, its role in the regulation of the parasite life cycle is poorly understood. Here we describe functional studies of a SUMO-specific protease (SENP) of P. falciparum , PfSENP1 (PFL1635w). Expression of the catalytic domain of PfSENP1 and bioche...
31 CitationsSource
#1Asli Ovat (Georgia Institute of Technology)H-Index: 2
#2Zhao Zhao Li (Georgia Institute of Technology)
Last. James C. PowersH-Index: 63
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A series of peptidyl α-ketoamides with the general structure Cbz-l-Leu-d,l-AA-CONH-R were synthesized and evaluated as inhibitors for the cysteine proteases calpain I, calpain II, and cathepsin B. Nucleobases, methylpiperazine, and dimethylaminoalkyl groups were incorporated into the primed region of the inhibitors to generate compounds that potentially cross the blood−brain barrier. Two of these compounds (Cbz-Leu-d,l-Abu-CONH-(CH2)3-adenin-9-yl and Cbz-Leu-d,l-Abu-CONH-(CH2)3-(4-methylpiperazi...
23 CitationsSource
#1Asli Ovat (Georgia Institute of Technology)H-Index: 2
#2Fanuel MuindiH-Index: 7
Last. James C. PowersH-Index: 63
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Aza-peptide Michael acceptors and epoxides with the general structure of YCO-Ala-Ala-AAsn-trans-CH═CHCOR and YCO-Ala-Ala-AAsn-EP-COR, respectively, are shown to be potent inhibitors of asparaginyl endopeptidases (legumains) from the bloodfluke, Schistosoma mansoni (SmAE), and the hard tick, Ixodes ricinus (IrAE). Structure−activity relationships (SARs) were determined for a set of 41 aza-peptide Michael acceptors and eight aza-peptide epoxides. Both enzymes prefer disubstituted amides to monosub...
28 CitationsSource
#1Aimee Shen (HHMI: Howard Hughes Medical Institute)H-Index: 29
#2Patrick J. Lupardus (HHMI: Howard Hughes Medical Institute)H-Index: 18
Last. Matthew Bogyo (HHMI: Howard Hughes Medical Institute)H-Index: 88
view all 7 authors...
Mechanistic and structural insights into the proteolytic activation of Vibrio cholerae MARTX toxin
65 CitationsSource