Review
Biochemistry & Molecular Biology
Martin Ian P. Malgapo, Maurine E. Linder
Summary: Protein palmitoylation is a post-translational modification method associated with various diseases, and identifying the protein substrates of zDHHC proteins is key to understanding their physiological and pathophysiological importance.
Article
Physiology
Angela R. R. Wild, Peter W. W. Hogg, Stephane Flibotte, Shruti Kochhar, Rocio B. B. Hollman, Kurt Haas, Shernaz X. X. Bamji
Summary: The reversible lipid modification protein S-palmitoylation has significant implications in various aspects of cellular function and diseases. However, the expression patterns of genes regulating palmitoylation in different human cell types and commonly used cell lines are poorly understood. To address this knowledge gap, we developed CellPalmSeq, a curated RNAseq database and webtool that visualizes the expression patterns of palmitoylation-related genes across various human cell types, tissues, and cell lines. This resource provides valuable insights into cellular physiology and disease, and can assist in selecting appropriate cell lines and interpreting results in studies involving protein S-palmitoylation.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yanli Sun, Haibo Lu, Xueyu Fang, Senhao Xiao, Feng Yang, Yantao Chen, Hongbo Wang, Xiaopeng Li, Jing Lu, Hua Lin, Cheng Luo, Kehao Zhao, Shijie Chen
Summary: Tumor suppressor p53-binding protein 1 (53BP1) plays a crucial role in DNA Damage Repair pathways and its dysregulation is associated with various diseases including cancer. Recent studies have identified a novel and effective 53BP1-TTD inhibitor DP308, disrupting the binding between 53BP1 and H4K20me2 peptide, showing promise as a potential tool for further optimization of biological functions and gene editing therapies.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Christine Salaun, Hiroya Takizawa, Alex Galindo, Kevin R. Munro, Jayde McLellan, Isamu Sugimoto, Tomotaka Okino, Nicholas C. O. Tomkinson, Luke H. Chamberlain
Summary: Protein S-acylation is a reversible post-translational modification that regulates the localization and function of cellular proteins. This study developed a high-throughput assay to screen for compounds that interfere with the autoacylation of zDHHC2, an enzyme involved in neuronal S-acylation pathways. Two compounds were identified that inhibited both zDHHC2 autoacylation and substrate S-acylation, providing potential tools for studying the cellular activities of zDHHC enzymes in S-acylation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Virology
Xiaojing Wen, Li Zhang, Qiang Liu, Xinyue Xiao, Weijin Huang, Youchun Wang
Summary: A high-throughput screening method was developed to identify compounds with inhibitory effects on Hantavirus. Cepharanthine, one of the identified compounds, showed promising activity in vitro and in vivo. These findings could potentially contribute to the treatment of Hantavirus infections.
Article
Biochemistry & Molecular Biology
Ruhani Sagar, Jinchao Lou, Michael D. Best
Summary: In this work, a bis-pyrene phospholipid probe was designed, synthesized, and applied for the detection of phospholipase A2 (PLA2) activity. The probe exhibited changes in pyrene monomer and excimer fluorescence intensities upon PLA2 action. Continuous fluorometric assays enabled the detection of multiple PLA2 enzymes and the inhibition of PLA2 activity by p-bromo phenacylbromide. Thin-layer chromatography and mass spectrometry analysis confirmed the hydrolysis of the probe by PLA2. The probe also showed cleavage by phospholipase C and D enzymes, although fluorescence changes were not observed. Overall, the developed bis-pyrene phospholipid probe is effective for the detection of PLA2 activity and can be used for inhibitor screening.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Giulia Alboreggia, Parima Udompholkul, Carlo Baggio, Maurizio Pellecchia
Summary: We introduce an innovative ligand discovery strategy using protein NMR-based screening of a combinatorial library of about 125,000 compounds arranged in 96 mixtures. This approach, based on sensitive solution protein NMR spectroscopy and chemical perturbation-based screening, followed by iterative synthesis, deconvolutions, and optimization, is shown to be useful in identifying initial binding molecules for difficult drug targets, such as those involved in protein-protein interactions. As an application, we report on the discovery of novel agents targeting the Bcl-2 family protein hMcl-1. This strategy has broad applicability and can be an effective screening approach for de novo ligand identification, especially for targets involved in protein-protein interactions.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Thahani S. Habeeb Mohammad, Yash Gupta, Cory T. Reidl, Vlad Nicolaescu, Haley Gula, Ravi Durvasula, Prakasha Kempaiah, Daniel P. Becker
Summary: The landscape of SARS-CoV-2 viral strains is dominated by the Delta and Omicron variants, with the latter showing high immune evasion and global circulation. In search of potential drugs against SARS-CoV-2, a library of substituted alpha-aminocyclobutanones was screened, resulting in the identification of derivatives with anti-SARS-CoV-2 activity, particularly against the Nsp13 helicase enzyme. These inhibitors exhibited higher activities against the Omicron variant than the wild-type strain, suggesting the potential of targeting Nsp13 helicase to combat aggressive variants. This work highlights the importance of cyclobutanones as medicinal chemistry scaffolds and the need for Nsp13 helicase inhibitors to address immune-evading variants.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Zhongyuan Luo, Daohai Du, Yanjun Liu, Tian Lu, Liping Liu, Hualiang Jiang, Kaixian Chen, Changliang Shan, Cheng Luo
Summary: A new high-throughput screening method was developed to discover G6PD inhibitors, with Wedelolactone identified as a strong inhibitor in a non-competitive, reversible manner, as confirmed by surface Plasmon Resonance assay. The study also showed the inhibitory effect of Wedelolactone on ovarian cancer cell proliferation through targeting G6PD.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Shivam A. Zaver, Alex J. Pollock, Vishant M. Boradia, Joshua J. Woodward
Summary: Recent research has identified c-di-AMP as an essential signaling molecule in various bacterial genera, with defects leading to severe physiological defects and virulence attenuation. A new method utilizing CnpB for high-throughput and sensitive quantification of c-di-AMP has been developed, providing a more affordable and sensitive alternative for studying bacterial cyclic dinucleotide physiology.
Article
Multidisciplinary Sciences
Sujata Bupp, Matthew Whittaker, Mari Lehtimaki, JuMe Park, Jessica Dement-Brown, Zhao-Hua Zhou, Steven Kozlowski
Summary: HAE is a rare genetic disease caused by deficiency or mutations in the C1-inhibitor gene, leading to acute attacks of edema and other symptoms. This study established the first physiological in vivo model to mimic acute HAE attacks using mice, and demonstrated that the HAE therapeutic ecallantide can prevent HAE attacks.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Medicinal
Victor Clausse, Yuhong Fang, Dingyin Tao, Harichandra D. Tagad, Hongmao Sun, Yuhong Wang, Surendra Karavadhi, Kelly Lane, Zhen-Dan Shi, Olga Vasalatiy, Christopher A. LeClair, Rebecca Eells, Min Shen, Samarjit Patnaik, Ettore Appella, Nathan P. Coussens, Matthew D. Hall, Daniel H. Appella
Summary: This study reports the discovery of new WIP1 modulators from a high-throughput screen, which can identify both inhibitors and activators. These hits have the potential to be used for the treatment of different cancers with varying P53 status.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2022)
Article
Infectious Diseases
Tung Tran, Kevin Chiem, Saumya Jani, Brock A. Arivett, David L. Lin, Rupali Lad, Veronica Jimenez, Mary B. Farone, Ginamarie Debevec, Radleigh Santos, Marc Giulianotti, Clemencia Pinilla, Marcelo E. Tolmasky
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2018)
Article
Neurosciences
Andrea Cippitelli, Gloria Brunori, Jennifer Schoch, Christopher J. Armishaw, Jinhua Wu, Nurulain T. Zaveri, Marc A. Giulianotti, Gregory S. Welmaker, Lawrence Toll
PSYCHOPHARMACOLOGY
(2018)
Article
Microbiology
Renee M. Fleeman, Ginamarie Debevec, Kirsten Antonen, Jessie L. Adams, Radleigh G. Santos, Gregory S. Welmaker, Richard A. Houghten, Marc A. Giulianotti, Lindsey N. Shaw
FRONTIERS IN MICROBIOLOGY
(2018)
Article
Chemistry, Medicinal
Katlyn A. Fleming, Katie T. Freeman, Mike D. Powers, Radleigh G. Santos, Ginamarie Debevec, Marc A. Giulianotti, Richard A. Houghten, Skye R. Doering, Clemencia Pinilla, Carrie Haskell-Luevano
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Rachel M. Sammons, Nicole A. Perry, Yangmei Li, Eun Jeong Cho, Andrea Piserchio, Diana P. Zamora-Olivares, Ranajeet Ghose, Tamer S. Kaoud, Ginamarie Debevec, Chandra Bartholomeusz, Vsevolod V. Gurevich, Tina M. Iverson, Marc Giulianotti, Richard A. Houghten, Kevin N. Dalby
ACS CHEMICAL BIOLOGY
(2019)
Editorial Material
Chemistry, Multidisciplinary
Marc A. Giulianotti, Lucie A. Low
PHARMACEUTICAL RESEARCH
(2020)
Article
Chemistry, Multidisciplinary
Lucie A. Low, Marc A. Giulianotti
PHARMACEUTICAL RESEARCH
(2020)
Article
Biochemical Research Methods
Eun Jeong Cho, Ashwini K. Devkota, Gabriel Stancu, Ramakrishna Edupunganti, Ginamarie Debevec, Marc Giulianotti, Richard Houghten, Garth Powis, Kevin N. Dalby
Article
Biochemistry & Molecular Biology
Xiaojuan Zhang, Radleigh Santos, Ginamarie Debevec, Danmeng Li, Ryan Schutte, Kien Pham, Chen Liu, David A. Ostrov, Marc Giulianotti
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2020)
Review
Infectious Diseases
Maria Magana, Muthuirulan Pushpanathan, Ana L. Santos, Leon Leanse, Michael Fernandez, Anastasios Ioannidis, Marc A. Giulianotti, Yiorgos Apidianakis, Steven Bradfute, Andrew L. Ferguson, Artem Cherkasov, Mohamed N. Seleem, Clemencia Pinilla, Cesar de la Fuente-Nunez, Themis Lazaridis, Tianhong Dai, Richard A. Houghten, Robert E. W. Hancock, George P. Tegos
LANCET INFECTIOUS DISEASES
(2020)
Article
Chemistry, Medicinal
Skye R. Doering, Katie Freeman, Ginamarie Debevec, Phaedra Geer, Radleigh G. Santos, Travis M. Lavoi, Marc A. Giulianotti, Clemencia Pinilla, Jon R. Appel, Richard A. Houghten, Mark D. Ericson, Carrie Haskell-Luevano
Summary: This study reports the discovery of first-in-class small molecule melanocortin agonists with selectivity for MC3R, which may serve as novel lead compounds to modulate states of dysregulated energy balance.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Mark D. Ericson, Skye R. Doering, Courtney M. Larson, Katie T. Freeman, Travis M. LaVoi, Haley M. Donow, Radleigh G. Santos, Rachel H. Cho, Zoe M. Koerperich, Marc A. Giulianotti, Clemencia Pinilla, Richard A. Houghten, Carrie Haskell-Luevano
Summary: A novel MC4R antagonist tetrapeptide sequence was identified, with 13 compounds possessing nanomolar antagonist potency at the MC4R, serving as potential leads for novel appetite-inducing therapies.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Virology
Ahmed A. Ramadan, Karthick Mayilsamy, Andrew R. McGill, Anandita Ghosh, Marc A. Giulianotti, Haley M. Donow, Shyam S. Mohapatra, Subhra Mohapatra, Bala Chandran, Robert J. Deschenes, Arunava Roy
Summary: The study found that palmitoylation of the S protein of SARS-CoV-2 is necessary for infection and palmitoylation-deficient mutants have defects in membrane fusion. DHHC9 palmitoyltransferase interacts with the spike protein and participates in its palmitoylation. Inhibition of DHHC9 results in reduced SARS-CoV-2 infection. In addition, inhibition of S protein palmitoylation could serve as a potential new intervention strategy against SARS-CoV-2.
Correction
Chemistry, Medicinal
Skye R. Doering, Katie Freeman, Ginamarie Debevec, Phaedra Geer, Radleigh G. Santos, Travis M. Lavoi, Marc A. Giulianotti, Clemencia Pinilla, Jon R. Appel, Richard A. Houghten, Mark D. Ericson, Carrie Haskell-Luevano
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Ahmed S. Ramadan, Lisa S. Kirouac, Amanda E. Sales Conniff, Karisa Serraneou, Medina Dzaferi, Sydni S. Schlosser, Laura S. Pendleton, Robert J. Deschenes