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Articles 1 - 6 of 6
Full-Text Articles in Physical Sciences and Mathematics
Identification Of Protein Palmitoylation Inhibitors From A Scaffold Ranking Library, Laura D. Hamel, Brian J. Lenhart, David A. Mitchell, Radleigh Santos, Marc A. Giulianotti, Robert J. Deschenes
Identification Of Protein Palmitoylation Inhibitors From A Scaffold Ranking Library, Laura D. Hamel, Brian J. Lenhart, David A. Mitchell, Radleigh Santos, Marc A. Giulianotti, Robert J. Deschenes
Mathematics Faculty Articles
The addition of palmitoyl moieties to proteins regulates their membrane targeting, subcellular localization, and stability. Dysregulation of the enzymes which catalyzed the palmitoyl addition and/or the substrates of these enzymes have been linked to cancer, cardiovascular, and neurological disorders, implying these enzymes and substrates are valid targets for pharmaceutical intervention. However, current chemical modulators of zDHHC PAT enzymes lack specificity and affinity, underscoring the need for screening campaigns to identify new specific, high affinity modulators. This report describes a mixture based screening approach to identify inhibitors of Erf2 activity. Erf2 is the Saccharomyces cerevisiae PAT responsible for catalyzing the palmitoylation …
Direct Phenotypic Screening In Mice: Identification Of Individual, Novel Antinociceptive Compounds From A Library Of 734 821 Pyrrolidine Bis-Piperazines, Richard A. Houghten, Michelle L. Ganno, Jay P. Mclaughlin, Colette T. Dooley, Shainnel O. Eans Torrey Pines Institute For Molecular Studies, Radleigh Santos, Travis Lavoi, Adel Nefzi, Greg Welmaker, Marc A. Giulianotti, Lawrence Toll
Direct Phenotypic Screening In Mice: Identification Of Individual, Novel Antinociceptive Compounds From A Library Of 734 821 Pyrrolidine Bis-Piperazines, Richard A. Houghten, Michelle L. Ganno, Jay P. Mclaughlin, Colette T. Dooley, Shainnel O. Eans Torrey Pines Institute For Molecular Studies, Radleigh Santos, Travis Lavoi, Adel Nefzi, Greg Welmaker, Marc A. Giulianotti, Lawrence Toll
Mathematics Faculty Articles
The hypothesis in the current study is that the simultaneous direct in vivo testing of thousands to millions of systematically arranged mixture-based libraries will facilitate the identification of enhanced individual compounds. Individual compounds identified from such libraries may have increased specificity and decreased side effects early in the discovery phase. Testing began by screening ten diverse scaffolds as single mixtures (ranging from 17 340 to 4 879 681 compounds) for analgesia directly in the mouse tail withdrawal model. The “all X” mixture representing the library TPI-1954 was found to produce significant antinociception and lacked respiratory depression and hyperlocomotor effects using …
Identification Of Tetrapeptides From A Mixture Based Positional Scanning Library That Can Restore Nm Full Agonist Function Of The L106p, I69t, I102s, A219v, C271y, And C271r Human Melanocortin-4 Polymorphic Receptors (Hmc4rs), Erica M. Haslach, Huisuo Huang, Marvin Dirain, Ginamarie Debevec, Phaedra Geer, Radleigh Santos, Marc Giulianotti, Clemencia Pinilla, Jon R. Appel, Skye R. Doering, Michael A. Walters, Richard A. Houghten, Carrie Haskell-Luevano
Identification Of Tetrapeptides From A Mixture Based Positional Scanning Library That Can Restore Nm Full Agonist Function Of The L106p, I69t, I102s, A219v, C271y, And C271r Human Melanocortin-4 Polymorphic Receptors (Hmc4rs), Erica M. Haslach, Huisuo Huang, Marvin Dirain, Ginamarie Debevec, Phaedra Geer, Radleigh Santos, Marc Giulianotti, Clemencia Pinilla, Jon R. Appel, Skye R. Doering, Michael A. Walters, Richard A. Houghten, Carrie Haskell-Luevano
Mathematics Faculty Articles
Human obesity has been linked to genetic factors and single nucleotide polymorphisms (SNPs). Melanocortin-4 receptor (MC4R) SNPs have been associated with up to 6% frequency in morbidly obese children and adults. A potential therapy for individuals possessing such genetic modifications is the identification of molecules that can restore proper receptor signaling and function. These compounds could serve as personalized medications improving quality of life issues as well as alleviating diseases symptoms associated with obesity including type 2 diabetes. Several hMC4 SNP receptors have been pharmacologically characterized in vitro to have a decreased, or a lack of response, to endogenous agonists …
Identification Of Beryllium-Dependent Peptides Recognized By Cd4+ T Cells In Chronic Beryllium Disease, Michael T. Falta, Clemencia Pinilla, Douglas G. Mack, Alex N. Tinega, Francis Crawford, Marc Giulianotti, Radleigh Santos, Gina M. Clayton, Yuxiao Wang, Xuewu Zhang, Lisa A. Maier, Philippa Marrack, John W. Kappler, Andrew P. Fontenot
Identification Of Beryllium-Dependent Peptides Recognized By Cd4+ T Cells In Chronic Beryllium Disease, Michael T. Falta, Clemencia Pinilla, Douglas G. Mack, Alex N. Tinega, Francis Crawford, Marc Giulianotti, Radleigh Santos, Gina M. Clayton, Yuxiao Wang, Xuewu Zhang, Lisa A. Maier, Philippa Marrack, John W. Kappler, Andrew P. Fontenot
Mathematics Faculty Articles
Chronic beryllium disease (CBD) is a granulomatous disorder characterized by an influx of beryllium (Be)-specific CD4+ T cells into the lung. The vast majority of these T cells recognize Be in an HLA-DP–restricted manner, and peptide is required for T cell recognition. However, the peptides that stimulate Be-specific T cells are unknown. Using positional scanning libraries and fibroblasts expressing HLA-DP2, the most prevalent HLA-DP molecule linked to disease, we identified mimotopes and endogenous self-peptides that bind to MHCII and Be, forming a complex recognized by pathogenic CD4+ T cells in CBD. These peptides possess aspartic and glutamic acid residues at …
The Mathematics Of A Successful Deconvolution: A Quantitative Assessment Of Mixture-Based Combinatorial Libraries Screened Against Two Formylpeptide Receptors, Radleigh Santos, Jon R. Appel, Marc Giulianotti, Bruce S. Edwards, Larry A. Sklar, Richard A. Houghten, Clemencia Pinilla
The Mathematics Of A Successful Deconvolution: A Quantitative Assessment Of Mixture-Based Combinatorial Libraries Screened Against Two Formylpeptide Receptors, Radleigh Santos, Jon R. Appel, Marc Giulianotti, Bruce S. Edwards, Larry A. Sklar, Richard A. Houghten, Clemencia Pinilla
Mathematics Faculty Articles
In the past 20 years, synthetic combinatorial methods have fundamentally advanced the ability to synthesize and screen large numbers of compounds for drug discovery and basic research. Mixture-based libraries and positional scanning deconvolution combine two approaches for the rapid identification of specific scaffolds and active ligands. Here we present a quantitative assessment of the screening of 32 positional scanning libraries in the identification of highly specific and selective ligands for two formylpeptide receptors. We also compare and contrast two mixture-based library approaches using a mathematical model to facilitate the selection of active scaffolds and libraries to be pursued for further …
Gm-Csf Production Allows The Identification Of Immunoprevalent Antigens Recognized By Human Cd4+ T Cells Following Smallpox Vaccination, Valeria A. Judkowski, Alcinette Bunying, Feng Ge, Jon R. Appel, Kingyee Law, Atima Sharma, Claudia Raja-Gabaglia, Patricia Norori, Radleigh Santos, Marc Giulianotti, Mark K. Slifka, Daniel C. Douek, Barney S. Graham, Clemencia Pinilla
Gm-Csf Production Allows The Identification Of Immunoprevalent Antigens Recognized By Human Cd4+ T Cells Following Smallpox Vaccination, Valeria A. Judkowski, Alcinette Bunying, Feng Ge, Jon R. Appel, Kingyee Law, Atima Sharma, Claudia Raja-Gabaglia, Patricia Norori, Radleigh Santos, Marc Giulianotti, Mark K. Slifka, Daniel C. Douek, Barney S. Graham, Clemencia Pinilla
Mathematics Faculty Articles
The threat of bioterrorism with smallpox and the broad use of vaccinia vectors for other vaccines have led to the resurgence in the study of vaccinia immunological memory. The importance of the role of CD4+ T cells in the control of vaccinia infection is well known. However, more CD8+ than CD4+ T cell epitopes recognized by human subjects immunized with vaccinia virus have been reported. This could be, in part, due to the fact that most of the studies that have identified human CD4+ specific protein-derived fragments or peptides have used IFN-γ production to evaluate vaccinia specific T cell responses. …