Search Results - "Geoghegan, Kieran F."

Selective stalling of human translation through small-molecule engagement of the ribosome nascent chain by Lintner, Nathanael G, McClure, Kim F, Petersen, Donna, Londregan, Allyn T, Piotrowski, David W, Wei, Liuqing, Xiao, Jun, Bolt, Michael, Loria, Paula M, Maguire, Bruce, Geoghegan, Kieran F, Huang, Austin, Rolph, Tim, Liras, Spiros, Doudna, Jennifer A, Dullea, Robert G, Cate, Jamie H D

“…Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in regulating the levels of plasma low-density lipoprotein cholesterol (LDL-C). Here, we…”
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Engineered stabilization and structural analysis of the autoinhibited conformation of PDE4 by Cedervall, Peder, Aulabaugh, Ann, Geoghegan, Kieran F., McLellan, Thomas J., Pandit, Jayvardhan

“…Significance Phosphodiesterase 4 (PDE4) is an essential contributor to intracellular signaling and an important drug target. We have used protein engineering,…”
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Rational Targeting of Active-Site Tyrosine Residues Using Sulfonyl Fluoride Probes by Hett, Erik C, Xu, Hua, Geoghegan, Kieran F, Gopalsamy, Ariamala, Kyne, Robert E, Menard, Carol A, Narayanan, Arjun, Parikh, Mihir D, Liu, Shenping, Roberts, Lee, Robinson, Ralph P, Tones, Michael A, Jones, Lyn H

“…This work describes the first rational targeting of tyrosine residues in a protein binding site by small-molecule covalent probes. Specific tyrosine residues…”
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Chemoproteomic profiling reveals that cathepsin D off-target activity drives ocular toxicity of β-secretase inhibitors by Zuhl, Andrea M., Nolan, Charles E., Brodney, Michael A., Niessen, Sherry, Atchison, Kevin, Houle, Christopher, Karanian, David A., Ambroise, Claude, Brulet, Jeffrey W., Beck, Elizabeth M., Doran, Shawn D., O’Neill, Brian T., am Ende, Christopher W., Chang, Cheng, Geoghegan, Kieran F., West, Graham M., Judkins, Joshua C., Hou, Xinjun, Riddell, David R., Johnson, Douglas S.

“…Inhibition of β-secretase BACE1 is considered one of the most promising approaches for treating Alzheimer’s disease. Several structurally distinct BACE1…”
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Activation of Liver AMPK with PF-06409577 Corrects NAFLD and Lowers Cholesterol in Rodent and Primate Preclinical Models by Esquejo, Ryan M., Salatto, Christopher T., Delmore, Jake, Albuquerque, Bina, Reyes, Allan, Shi, Yuji, Moccia, Rob, Cokorinos, Emily, Peloquin, Matthew, Monetti, Mara, Barricklow, Jason, Bollinger, Eliza, Smith, Brennan K., Day, Emily A., Nguyen, Chuong, Geoghegan, Kieran F., Kreeger, John M., Opsahl, Alan, Ward, Jessica, Kalgutkar, Amit S., Tess, David, Butler, Lynne, Shirai, Norimitsu, Osborne, Timothy F., Steinberg, Gregory R., Birnbaum, Morris J., Cameron, Kimberly O., Miller, Russell A.

“…Dysregulation of hepatic lipid and cholesterol metabolism is a significant contributor to cardiometabolic health, resulting in excessive liver lipid…”
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Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia by Mansour, Mahmoud N, Seddon, Andrew P, Hoth, Lise R, Xia, Donghui, Geoghegan, Kieran F, Griffor, Matthew C, Subashi, Timothy A, Shenolikar, Shirish, Danley, Dennis E, Ammirati, Mark J, McGrath, Katherine M, Culp, Jeffrey S, Hawkins, Julie L, Varghese, Alison H, Qiu, Xiayang, Warren, Laurie C, Cunningham, David, Stutzman-Engwall, Kim J

“…Proprotein convertase subtilisin kexin type 9 (PCSK9) lowers the abundance of surface low-density lipoprotein (LDL) receptor through an undefined mechanism…”
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Selective mechanism-based inactivation of CYP3A4 by CYP3cide (PF-04981517) and its utility as an in vitro tool for delineating the relative roles of CYP3A4 versus CYP3A5 in the metabolism of drugs by Walsky, Robert L, Obach, R Scott, Hyland, Ruth, Kang, Ping, Zhou, Sue, West, Michael, Geoghegan, Kieran F, Helal, Christopher J, Walker, Gregory S, Goosen, Theunis C, Zientek, Michael A

“…CYP3cide (PF-4981517; 1-methyl-3-[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]-4-[(3S)-3-piperidin-1-ylpyrrolidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine) is a…”
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Pharmacologic inhibition of site 1 protease activity inhibits sterol regulatory element-binding protein processing and reduces lipogenic enzyme gene expression and lipid synthesis in cultured cells and experimental animals by Hawkins, Julie L, Robbins, Michael D, Warren, Laurie C, Xia, Donghui, Petras, Stephen F, Valentine, James J, Varghese, Alison H, Wang, Ing-Kae, Subashi, Timothy A, Shelly, Lorraine D, Hay, Bruce A, Landschulz, Katherine T, Geoghegan, Kieran F, Harwood, Jr, H James

“…Sterol regulatory element-binding proteins (SREBPs) are major transcriptional regulators of cholesterol, fatty acid, and glucose metabolism. Genetic disruption…”
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A tag-free collisionally induced fragmentation approach to detect drug-adducted proteins by mass spectrometry by Ballard, T. Eric, Dahal, Upendra P., Bessire, Andrew J., Schneider, Richard P., Geoghegan, Kieran F., Vaz, Alfin D. N.

“…Rationale The covalent modification of proteins by toxicants, new chemical entities or drug molecules, either by metabolic activation or the presence of…”
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Correction: Selective stalling of human translation through small-molecule engagement of the ribosome nascent chain by Lintner, Nathanael G, McClure, Kim F, Petersen, Donna, Londregan, Allyn T, Piotrowski, David W, Wei, Liuqing, Xiao, Jun, Bolt, Michael, Loria, Paula M, Maguire, Bruce, Geoghegan, Kieran F, Huang, Austin, Rolph, Tim, Liras, Spiros, Doudna, Jennifer A, Dullea, Robert G, Cate, Jamie H D

“…[This corrects the article DOI: 10.1371/journal.pbio.2001882.]…”
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Kinetic Analysis of Estrogen Receptor/Ligand Interactions by Rich, Rebecca L., Hoth, Lise R., Geoghegan, Kieran F., Brown, Thomas A., LeMotte, Peter K., Simons, Samuel P., Hensley, Preston, Myszka, David G.

“…Surface plasmon resonance biosensor technology was used to directly measure the binding interactions of small molecules to the ligand-binding domain of human…”
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Biochemical applications of mass spectrometry in pharmaceutical drug discovery by Geoghegan, Kieran F., Kelly, Michele A.

“…Biochemical applications of mass spectrometry (MS) are important in the pharmaceutical industry. They comprise compositional analyses of biomolecules,…”
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A library approach to rapidly discover photoaffinity probes of the mRNA decapping scavenger enzyme DcpS by Xu, Hua, Hett, Erik C, Gopalsamy, Ariamala, Parikh, Mihir D, Geoghegan, Kieran F, Kyne, Jr, Robert E, Menard, Carol A, Narayanan, Arjun, Robinson, Ralph P, Johnson, Douglas S, Tones, Michael A, Jones, Lyn H

“…Despite its diverse applications, such as identification of the protein binding partners of small molecules and investigation of intracellular drug-target…”
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Chemoproteomic Analysis of Intertissue and Interspecies Isoform Diversity of AMP-activated Protein Kinase (AMPK) by Wu, Jiang, Puppala, Dinesh, Feng, Xidong, Monetti, Mara, Lapworth, Amanda Lee, Geoghegan, Kieran F.

“…AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme that senses and governs changes in the cellular energy balance represented by concentrations of…”
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Discovery of a JAK3-Selective Inhibitor: Functional Differentiation of JAK3-Selective Inhibition over pan-JAK or JAK1-Selective Inhibition by Telliez, Jean-Baptiste, Dowty, Martin E, Wang, Lu, Jussif, Jason, Lin, Tsung, Li, Li, Moy, Erick, Balbo, Paul, Li, Wei, Zhao, Yajuan, Crouse, Kimberly, Dickinson, Caitlyn, Symanowicz, Peter, Hegen, Martin, Banker, Mary Ellen, Vincent, Fabien, Unwalla, Ray, Liang, Sidney, Gilbert, Adam M, Brown, Matthew F, Hayward, Matthew, Montgomery, Justin, Yang, Xin, Bauman, Jonathan, Trujillo, John I, Casimiro-Garcia, Agustin, Vajdos, Felix F, Leung, Louis, Geoghegan, Kieran F, Quazi, Amira, Xuan, Dejun, Jones, Lyn, Hett, Erik, Wright, Katherine, Clark, James D, Thorarensen, Atli

“…PF-06651600, a newly discovered potent JAK3-selective inhibitor, is highly efficacious at inhibiting γc cytokine signaling, which is dependent on both JAK1 and…”
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Emerging Methods in Chemoproteomics with Relevance to Drug Discovery by Nguyen, Chuong, West, Graham M, Geoghegan, Kieran F

“…A powerful interplay exists between the recognition of gene families, sensitive techniques in proteomics, and the interrogation of protein function using…”
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Mapping the Binding Site of BMS-708163 on γ-Secretase with Cleavable Photoprobes by Gertsik, Natalya, Am Ende, Christopher W, Geoghegan, Kieran F, Nguyen, Chuong, Mukherjee, Paramita, Mente, Scot, Seneviratne, Uthpala, Johnson, Douglas S, Li, Yue-Ming

“…γ-Secretase, a four-subunit transmembrane aspartic proteinase, is a highly valued drug target in Alzheimer's disease and cancer. Despite significant progress…”
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Modification of Amino Groups by Geoghegan, Kieran F

“…Chemical modification of amino groups in proteins serves a diversity of preparative and analytical purposes. The most prominent is to attach nonpeptide groups…”
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Phosphoproteomic evaluation of pharmacological inhibition of leucine‐rich repeat kinase 2 reveals significant off‐target effects of LRRK‐2‐IN‐1 by Luerman, Gregory C., Nguyen, Chuong, Samaroo, Harry, Loos, Paula, Xi, Hualin, Hurtado‐Lorenzo, Andres, Needle, Elie, Stephen Noell, G., Galatsis, Paul, Dunlop, John, Geoghegan, Kieran F., Hirst, Warren D.

“…Genetic mutations in leucine‐rich repeat kinase 2 (LRRK2) have been linked to autosomal dominant Parkinson's disease. The most prevalent mutation, G2019S,…”
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Site-directed conjugation of nonpeptide groups to peptides and proteins via periodate oxidation of a 2-amino alcohol. Application to modification at N-terminal serine by Geoghegan, Kieran F, Stroh, Justin G

“…The 2-amino alcohol structure -CH(NH2)CH(OH)- exists in proteins and peptides in N-terminal Ser or Thr and in hydroxylysine. Its very rapid oxidation by…”
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