Article
Chemistry, Medicinal
Hao Zhang, Hao-Chi Hsu, Shoshanna C. Kahne, Ryoma Hara, Wenhu Zhan, Xiuju Jiang, Kristin Burns-Huang, Tierra Ouellette, Toshihiro Imaeda, Rei Okamoto, Masanori Kawasaki, Mayako Michino, Tzu-Tshin Wong, Akinori Toita, Takafumi Yukawa, Francesca Moraca, Jeremie Vendome, Priya Saha, Kenjiro Sato, Kazuyoshi Aso, John Ginn, Peter T. Meinke, Michael Foley, Carl F. Nathan, K. Heran Darwin, Huilin Li, Gang Lin
Summary: Current treatment of tuberculosis (TB) typically lasts at least 6 months, with the latent Mycobacterium tuberculosis (Mtb) being tolerant to most anti-TB drugs. A key hypothesis is that drugs targeting the Mtb proteasome (Mtb20S) may shorten treatment time when used in combination with conventional drugs. A series of macrocyclic peptides, including macrocycle 6, have been developed that selectively target the Mtb20S and have the potential to be developed as anti-TB therapeutics.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Emily S. Murzinski, Ishika Saha, Hui Ding, David Strugatsky, Ryan A. Hollibaugh, Haixia Liu, Peter Tontonoz, Patrick G. Harran
Summary: Ghrelin is a hormone that plays a crucial role in regulating food intake, growth hormone secretion, and insulin secretion. A medicinal chemistry campaign led to the discovery of small lipopeptidomimetics that inhibit GOAT in vitro. The study also synthesized heterocyclic inhibitors that compete at the acyl coenzyme A binding site.
Article
Endocrinology & Metabolism
Jui-Hsia Weng, Peter David Koch, Harding Luan, Ho-Chou Tu, Kenichi Shimada, Iris Ngan, Richard Ventura, Ruomu Jiang, Timothy J. Mitchison
Summary: The study demonstrates that the anti-inflammatory effects of colchicine are mediated indirectly through the release of hepatokines such as GDF15, rather than through direct action on immune cells. This suggests that the efficacy and safety of colchicine depend on its selective action on hepatocytes, revealing a new axis of liver-myeloid cell communication. Plasma GDF15 levels and myeloid cell SHP-1 activity may serve as useful pharmacodynamic biomarkers of colchicine action.
Article
Medicine, Research & Experimental
Ester Lopez, Ebene R. Haycroft, Amy Adair, Francesca L. Mordant, Matthew T. O'Neill, Phillip Pymm, Samuel J. Redmond, Wen Shi Lee, Nicholas A. Gherardin, Adam K. Wheatley, Jennifer A. Juno, Kevin J. Selva, Samantha K. Davis, Samantha L. Grimley, Leigh Harty, Damian F. J. Purcell, Kanta Subbarao, Dale Godfrey, Stephen J. Kent, Wai-Hong Tham, Amy W. Chung
Summary: This study introduces a new rapid multiplex assay for measuring SARS-CoV-2 antibodies that can evaluate multiple RBD natural variants, filling a major gap in SARS-CoV-2 research and providing a method for selecting complementary monoclonal antibody candidates and rapidly identifying immune escape to emerging RBD variants following vaccination or natural infection.
Article
Biochemistry & Molecular Biology
Trishna Saha Detroja, Abraham O. Samson
Summary: Arginases are overexpressed in human diseases, making them important targets for developing anti-aging and antineoplastic drugs. In this study, a virtual screening of 2115 FDA-approved drug molecules was conducted to identify potential arginase ligands. The results showed that half of the top 30 potential drugs are already used clinically for various conditions, validating the virtual screening approach. The three identified categories of potential arginase ligands greatly expand the selectivity of arginase inhibition.
Article
Biochemistry & Molecular Biology
Adam J. Middleton, Joan Teyra, Jingyi Zhu, Sachdev S. Sidhu, Catherine L. Day
Summary: This study identified protein-based reagents called UbVs that bind tightly to Ube2k, inhibiting its function. The unique binding site of UbVs suggests a potential target for inhibiting Ube2k and other E2 enzymes. Crystal structures revealed the mechanisms of UbVs blocking both ubiquitin charging of the E2 enzyme and E3-catalyzed ubiquitin transfer.
ACS CHEMICAL BIOLOGY
(2021)
Article
Oncology
Talar Tokatlian, Grace E. Asuelime, Jee-Young Mock, Breanna DiAndreth, Shruti Sharma, Dora Toledo Warshaviak, Mark E. Daris, Kristian Bolanos, Breanna L. Luna, Martin S. Naradikian, Kiran Deshmukh, Agnes E. Hamburger, Alexander Kamb
Summary: This study developed a dual-receptor system that can target mesothelin expressed in both tumor and normal tissues, reducing the risk of serious inflammation caused by the treatment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Chemistry, Applied
Zuzana Meszaros, Lucie Petraskova, Natalia Kulik, Helena Pelantova, Pavla Bojarova, Vladimir Kren, Kristyna Slamova
Summary: Fungal beta-N-acetylhexosaminidases are important tools for the synthesis of natural and modified oligosaccharides and glycoconjugates. In this study, the enzyme from Aspergillus oryzae was engineered to shift its reaction from hydrolysis to transglycosylation. Nine mutant variants of the enzyme were designed and tested, and one variant (V306W/Y445N AoHex) showed superior transglycosidase activity with a transglycosylation-to-hydrolysis ratio greater than 110, which is unique among similar mutants.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Education & Educational Research
Elizabeth A. Sanders, Molly H. Goldstein, Justin L. Hess
Summary: This study aimed to identify course characteristics that influence how students experience human-centered design. The findings suggested that most students did not prioritize human-centered design approaches during the course. However, students who demonstrated human-centered design approaches integrated user research into their design process, valued communication, and expressed feeling a tension between user information and course requirements.
INTERNATIONAL JOURNAL OF TECHNOLOGY AND DESIGN EDUCATION
(2023)
Article
Biochemistry & Molecular Biology
R. H. P. van Neer, P. K. Dranchak, L. Liu, M. Aitha, B. Queme, H. Kimura, T. Katoh, K. P. Battaile, S. Lovell, J. Inglese, H. Suga
Summary: By reconfiguring the structure of tRNA, we have successfully incorporated N-methylated amino acids into peptide chains. By utilizing RaPID display technology, we have identified N-methylated macrocyclic peptides with potential bioactivity and conducted structural and functional studies.
ACS CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Physical
Xander Schaapkens, Joel H. Holdener, Jens Tolboom, Eduard O. Bobylev, Joost N. H. Reek, Tiddo J. Mooibroek
Summary: Designing compounds for the selective molecular recognition of carbohydrates is a challenging task for supramolecular chemists. Macrocyclic compounds incorporating isophtalamide or bisurea spacers have proven effective for selective recognition of all-equatorial carbohydrates. The octa-urea [Pd2L4](4+) cage complex shows excellent selectivity towards n-octyl-alpha-D-Mannoside with inhibited binding of n-octyl glycosides by small anions like NO3- and BF4-.
Article
Biochemistry & Molecular Biology
Daniel J. Baillache, Teresa Valero, Alvaro Lorente-Macias, David Jonathan Bennett, Richard J. R. Elliott, Neil O. Carragher, Asier Unciti-Broceta
Summary: This study explored antiproliferative compounds for GBM treatment and established structure-antiproliferative activity relationships through the synthesis and screening of small compound libraries. Through a series of design, synthesis, and screening, potent CSF-1R inhibitors with significant antiproliferative activity were discovered.
RSC MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Xin-Ying Yuan, Chun -Hong Song, Xiu-Juan Liu, Xiao Wang, Mei-Qi Jia, Wang Wang, Wen-Bo Liu, Xiang-Jing Fu, Cheng-Yun Jin, Jian Song, Sai-Yang Zhang
Summary: In this study, N-benzylarylamide-dithiocarbamate based derivatives were synthesized and tested for their anticancer activities. Compound I-25 (also known as MY-943) showed potent inhibitory effects against multiple cancer cells, and induced cell cycle arrest, apoptosis, and inhibition of cell migration. The compound effectively inhibited tubulin polymerization and suppressed LSD1 activity. Molecular docking studies revealed the binding modes of compound I-25 with tubulin and LSD1. In vivo experiments demonstrated that compound I-25 effectively reduced the weight and volume of gastric cancer without noticeable toxicity. This study highlights the potential of N-benzylarylamide-dithiocarbamate derivatives as dual inhibitors targeting tubulin polymerization and LSD1 in gastric cancers.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Rahul D. Jawarkar, Magdi E. A. Zaki, Sami A. Al-Hussain, Aamal A. Al-Mutairi, Abdul Samad, Nobendu Mukerjee, Arabinda Ghosh, Vijay H. Masand, Long Chiau Ming, Summya Rashid
Summary: Due to the high risk of drug development failure and the huge costs involved, repurposing existing drugs has become more popular. In this study, QSAR modelling was used to identify structural features necessary for ACE2 inhibitory activity. The developed model yielded previously undisclosed features and provided novel mechanistic interpretations. The QSAR model predicted the ACE2 inhibitory activity of 1615 compounds, leading to the discovery of a potential hit molecule with significant inhibitory activity.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Aung Khine Linn, Nitchakan Samainukul, Somsri Sakdee, Chonthicha Butnampetch, Hui-Chun Li, Chanan Angsuthanasombat, Gerd Katzenmeier
Summary: The study found that the N-terminal tag played a crucial role in enhancing the expression of Helicobacter pylori VacA variants. Full-length VacA-m1 and the 33-kDa domain required N-terminal extension for efficient expression, while the 55-kDa domain could be expressed with either N or C-terminal extension. Despite higher membrane-perturbing and cytotoxic activities of VacA-m1 compared to VacA-m2, further research is needed to explore the differences between the domains.
PROTEIN AND PEPTIDE LETTERS
(2021)
