Article
Multidisciplinary Sciences
Neil J. Rzechorzek, Simone Kunzelmann, Andrew G. Purkiss, Mariana Silva Dos Santos, James I. MacRae, Ian A. Taylor, Kasper Fugger, Stephen C. West
Summary: This study presents the crystal structures and catalytic process of DNPH1, providing important insights for inhibitor design. Inactivation of DNPH1 increases the incorporation of hmdU into DNA, making BRCA-deficient cells more sensitive to PARP inhibitors.
NATURE COMMUNICATIONS
(2023)
Review
Immunology
Yoke Chan Chow, Hok Chai Yam, Baskaran Gunasekaran, Weng Yeen Lai, Weng Yue Wo, Tarun Agarwal, Yien Yien Ong, Siew Lee Cheong, Sheri-Ann Tan
Summary: Porphyromonas gingivalis, a major pathogenic bacterium involved in periodontitis, utilizes gingipain R and bacterial peptidyl arginine deiminase to citrullinate host proteins, leading to the development of non-communicable diseases. Inhibiting these enzymes can provide new therapeutic solutions for periodontitis and diseases involving bacterial citrullination.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Immunology
Dibya Sundar Padhy, Partha Palit, Abu Md Ashif Ikbal, Nirupam Das, Dilip Kumar Roy, Sugato Banerjee
Summary: Peptidyl arginine deiminases (PADs) are enzymes that irreversibly citrullinate arginine residues of protein in the presence of calcium ions. Increased PAD expression has been linked to various inflammatory diseases. Factors such as intracellular calcium levels, oxidative stress, and proinflammatory cytokines contribute to the elevation of PAD enzyme expression. PAD inhibitors derived from natural or synthetic sources show promise as a novel therapeutic approach for inflammatory disorders. This review discusses the pathological role of PAD in inflammatory diseases, factors triggering PAD expression, epigenetic regulation, and the therapeutic potential of PAD inhibitors.
INFLAMMOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Maria-Soledad Orellana, Gonzalo A. Jana, Maximiliano Figueroa, Jose Martinez-Oyanedel, Fabiola E. Medina, Estefania Tarifeno-Saldivia, Marcell Gatica, Maria Angeles Garcia-Robles, Nelson Carvajal, Elena Uribe
Summary: Arginase and agmatinase have similarities, but show different specificities for their substrates, with loop A and loop B playing crucial roles in the specificity of arginase.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Darshali P. Thakker, Rajnish Narayanan
Summary: Bacterial-based cancer immunotherapy is gaining attention for its unique mechanism in anti-cancer immune responses. Lactic acid bacteria, with their bioactive chemicals, have shown antitumor properties and can be used as a potential treatment for cancer. Understanding arginine metabolism in LAB and cancer cells could lead to new therapeutic targets. This review proposes an arginine deiminase expression system to improve cancer therapy.
Article
Biochemistry & Molecular Biology
Yurui Zhang, Nils Marechal, Matthijs J. van Haren, Nathalie Troffer-Charlier, Vincent Cura, Jean Cavarelli, Nathaniel I. Martin
Summary: The study investigates the impact of acetylation of Lys(18) in the histone H3 tail peptide on peptide recognition by the protein methyltransferase CARM1. Structural studies provide new insights into the binding of the H3 peptide within the enzyme active site, revealing that acetylation of Lys(18) leads to additional interactions and increased affinity, informing the development of peptidomimetic CARM1 inhibitors.
Article
Immunology
Maria Teresa Martin Monreal, Alexandra Stripp Rebak, Laura Massarenti, Santanu Mondal, Ladislav Senolt, Niels Odum, Michael L. Nielsen, Paul R. Thompson, Claus H. Nielsen, Dres Damgaard
Summary: Citrullination plays a role in breaking self-tolerance in anti-CCP-positive rheumatoid arthritis, with PAD2 and PAD4 being key pathogenic factors. Inhibitors like AFM-30a and GSK199 show potential in inhibiting citrullination, with AFM-30a being an efficient inhibitor of PAD2 and a combination of AFM-30a and GSK199 showing promise in inhibiting PAD activity without cytotoxic effects seen in BB-Cl-amidine.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Medicinal
David C. McKinney, Brian J. McMillan, Matthew Ranaghan, Jamie A. Moroco, Merissa Brousseau, Zachary Mullin-Bernstein, Meghan O'Keefe, Patrick McCarren, Michael F. Mesleh, Kathleen M. Mulvaney, Foxy Robinson, Ritu Singh, Besnik Bajrami, Florence F. Wagner, Robert Hilgraf, Martin J. Drysdale, Arthur J. Campbell, Adam Skepner, David E. Timm, Dale Porter, Virendar K. Kaushik, William R. Sellers, Alessandra Ianari
Summary: PRMT5 and its substrate adaptor proteins are essential for methylation of various substrates, including histones and spliceosome complexes. A compound series has been developed that can disrupt PRMT5-Riok1 complexes by binding to the PRMT5-PBM interface, providing a potential new approach for developing selective PRMT5 inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
David Vrbata, Marcela Filipova, Marina R. Tavares, Jakub Cerveny, Miluse Vlachova, Milada Sirova, Helena Pelantova, Lucie Petraskova, Ladislav Bumba, Rafal Konefal, Tomas Etrych, Vladimir Kren, Petr Chytil, Pavla Bojarova
Summary: Galectin-3 plays a role in cancer-related metabolic processes. Inhibiting overexpressed Galectin-3, such as with beta-galactoside-based inhibitors, holds promise for cancer treatment. A library of inhibitors was synthesized and displayed on a suitable biocompatible carrier to enhance affinity for Gal-3. One of the candidates exhibited strong inhibitory effects in cancer cells and shows potential for Gal-3-associated cancer therapy.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Joshua J. Hamey, Sinja Rakow, Caroline Bouchard, Johanna M. Senst, Peter Kolb, Uta-Maria Bauer, Marc R. Wilkins, Gene Hart-Smith
Summary: PRMT6 catalyzes the asymmetric dimethylation of arginines on substrate proteins, including histone H3, affecting gene regulation. This study systematically characterized PRMT6's substrate recognition motif, showing broad specificity and a preference for the RG motif. Despite efficient methylation at H3R2, PRMT6 tolerates various amino acid substitutions in the H3 peptide, with preference for positively charged and bulky residues near the target arginine.
Article
Chemistry, Medicinal
Khuchtumur Bum-Erdene, Patrick M. Collins, Matthew W. Hugo, Somayeh S. Tarighat, Fei Fei, Chandan Kishor, Hakon Leffler, Ulf J. Nilsson, John Groffen, I. Darren Grice, Nora Heisterkamp, Helen Blanchard
Summary: In this study, novel Galectin-3 antagonists with enhanced affinity and selectivity were designed and synthesized. Experimental results demonstrated the specific inhibition of Galectin-3-induced BCP-ALL cell agglutination and decreased viability of ALL cells. Therefore, these compounds show promise as important leads for cancer therapeutics.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Mukul Mahanti, Kumar Bhaskar Pal, Rohit Kumar, Markus Schulze, Hakon Leffler, Derek T. Logan, Ulf J. Nilsson
Summary: The sulfur oxidation state of galactoside ligands affects the thermodynamics and structure of their interactions with galectin-3.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Zhiyong Yin, Daniel Baer, Bertolt Gust, Jeroen S. Dickschat
Summary: This study investigated the substrate scope of nine dehydratases involved in secondary metabolite biosynthesis, in addition to FabZ from fatty acid biosynthesis, using a panel of N-acetylcysteamine (SNAC) thioesters. The best performing enzyme, BorDH2, was used in kinetic resolutions.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Shoko Inatani, Motoki Ochi, Kohnosuke Kinoshita, Jun-ichi Yamaguchi, Hiromi Endo
Summary: TP0473292 is an ester prodrug that enhances the oral bioavailability of the hydrophilic glutamate analog TP0178894, and functions as an antidepressant. Despite rapid hydrolysis in the intestine, TP0473292 achieved good oral bioavailability of TP0178894 in rats and monkeys.
DRUG METABOLISM AND DISPOSITION
(2023)
Article
Biotechnology & Applied Microbiology
Kei Yamamoto, Yosuke Masakari, Yasuko Araki, Atsushi Ichiyanagi, Kotaro Ito
Summary: This study aimed to develop an enzyme that could specifically detect citrulline and successfully improved the specific dehydrogenase activity by introducing a mutation. The enzymatic detection system using this enzyme can effectively detect citrulline in human blood.
Article
Biochemistry & Molecular Biology
Mikhail Marchenko, Andrew Thomson, Terri N. Ellis, Bryan Knuckley, Corey P. Causey
BIOORGANIC & MEDICINAL CHEMISTRY
(2015)
Article
Chemistry, Applied
Hao C. Nguyen, Min Wang, Andrew Salsburg, Bryan Knuckley
ACS COMBINATORIAL SCIENCE
(2015)
Article
Biochemical Research Methods
Elle D. James, Bryan Knuckley, Norah Alqahtani, Suheel Porwal, Jisun Ban, Jonathan A. Karty, Rajesh Viswanathan, Amy L. Lane
ACS SYNTHETIC BIOLOGY
(2016)
Article
Biochemistry & Molecular Biology
Charles A. Soares, Bryan Knuckley
BIOCHEMICAL JOURNAL
(2016)
Article
Dermatology
Marie-Claire Mechin, Laura Cau, Marie-Florence Galliano, Sylvie Daunes-Marion, Stephane Poigny, Jean-Louis Vidaluc, Sandrine Bessou-Touya, Hidenari Takahara, Guy Serre, Helene Duplan, Michel Simon
JOURNAL OF DERMATOLOGICAL SCIENCE
(2016)
Article
Biochemistry & Molecular Biology
Shinya Saijo, Anna Nagai, Saya Kinjo, Ryutaro Mashimo, Megumi Akimoto, Kenji Kizawa, Toshiki Yabe-Wada, Nobutaka Shimizu, Hidenari Takahara, Masaki Unno
JOURNAL OF MOLECULAR BIOLOGY
(2016)
Article
Dermatology
Laura Cau, Valerie Pendaries, Emeline Lhuillier, Paul R. Thompson, Guy Serre, Hidenari Takahara, Marie-Claire Mechin, Michel Simon
JOURNAL OF DERMATOLOGICAL SCIENCE
(2017)
Article
Dermatology
Chiung-Yueh Hsu, Geraldine Gasc, Anne-Aurelie Raymond, Odile Burlet-Schiltz, Hidenari Takahara, Guy Serre, Marie-Claire Mechin, Michel Simon
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2017)
Article
Biochemistry & Molecular Biology
Christina J. Dreyton, Bryan Knuckley, Justin E. Jones, Daniel M. Lewallen, Paul R. Thompson
Article
Biochemistry & Molecular Biology
Andrew Thomson, Sean O'Connor, Bryan Knuckley, Corey P. Causey
BIOORGANIC & MEDICINAL CHEMISTRY
(2014)
Article
Biochemistry & Molecular Biology
Akira Shimizu, Kenji Handa, Tomonori Honda, Naoki Abe, Toshio Kojima, Hidenari Takahara
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY
(2014)
Article
Biochemistry & Molecular Biology
Sarah A. Mann, Andrew Salsburg, Corey P. Causey, Bryan Knuckley
BIOORGANIC & MEDICINAL CHEMISTRY
(2019)
Article
Dermatology
Laura Cau, Hidenari Takahara, Paul R. Thompson, Guy Serre, Marie-Claire Mechin, Michel Simon
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Sarah A. Mann, Megan K. DeMart, Braidy May, Corey P. Causey, Bryan Knuckley
BIOCHEMICAL JOURNAL
(2020)
Article
Biochemistry & Molecular Biology
Mollie A. Brekker, Tala Sartawi, Tina M. Sawatzky, Corey P. Causey, Fatima Khwaja Rehman, Bryan Knuckley
Summary: Protein arginine methyltransferases (PRMTs) are enzymes that transfer a methyl group to arginine residues within proteins. Different types of methylated products can lead to increased or decreased transcription of cancer-related genes in certain cancers, suggesting that PRMT family members may be potential therapeutic targets. Peptide-based compounds, traditionally used to target PRMTs, suffer from poor stability and short half-lives. On the other hand, peptoids, peptide-mimetics composed of N-substituted glycine monomers, have improved stability and longer half-lives. This study reports the development of a bioavailable, peptoid-based PRMT1 inhibitor that induces cell death in specific cancer cell lines without significant impact on normal cells, suggesting it has less toxicity as a cytostatic agent.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)