Article
Multidisciplinary Sciences
Xinyuan Lei, Hsinyu Lin, Jieqi Wang, Zhanpeng Ou, Yi Ruan, Ananthan Sadagopan, Weixiong Chen, Shule Xie, Baisheng Chen, Qunxing Li, Jue Wang, Huayue Lin, Xiaofeng Zhu, Xiaoqing Yuan, Tian Tian, Xiaobin Lv, Sha Fu, Xiaorui Zhu, Jian Zhou, Guokai Pan, Xin Xia, Bakhos A. Tannous, Soldano Ferrone, Song Fan, Jinsong Li
Summary: The researchers found that rapid mitochondrial fission activates the ER-stress response, leading to reduced MHC-I complex formation and cell surface expression in cancer cells. Inhibition of mitochondrial fission increases MHC-I expression and enhances the efficacy of immunotherapy.
NATURE COMMUNICATIONS
(2022)
Article
Veterinary Sciences
A. P. Vodenicharov, M. Dimitrova, N. S. Tsandev, I. S. Stefanov
Summary: The distribution of TPPI activity in porcine lumbar spinal ganglia was studied using enzyme histochemistry, showing strong reaction in small neurons, satellite ganglia cells, and some nerve fibers, suggesting TPPI actively participates in the functions of all the neuronal structures in LSG.
POLISH JOURNAL OF VETERINARY SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Ronan P. Hanley, David Y. Nie, John R. Tabor, Fengling Li, Amin Sobh, Chenxi Xu, Natalie K. Barker, David Dilworth, Taraneh Hajian, Elisa Gibson, Magdalena M. Szewczyk, Peter J. Brown, Dalia Barsyte-Lovejoy, Laura E. Herring, Gang Greg Wang, Jonathan D. Licht, Masoud Vedadi, Cheryl H. Arrowsmith, Lindsey I. James
Summary: Nuclear receptor-binding SET domain-containing 2 (NSD2) is involved in gene regulation by dimethylating lysine 36 of histone 3 (H3K36me2). UNC8153 is a novel NSD2-targeted degrader that effectively reduces NSD2 protein and H3K36me2 levels. It works by degrading NSD2 through a unique mechanism and has demonstrated positive effects on pathological phenotypes in multiple myeloma cells.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Medicinal
Carlos Moreno-Yruela, Christian A. Olsen
Summary: This study highlights the importance of thorough kinetic investigation in the development of selective HDAC probes. Potent inhibitors of HDACs 1-3 often display slow-binding kinetics, and this study compares the potencies and selectivities of slow-binding inhibitors measured by discontinuous and continuous assays.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Neil D. Rawlings, Alex Bateman
Summary: The MEROPS website and database classify proteolytic enzymes and protein inhibitors based on biochemical and biological properties, creating a hierarchy with levels such as protein species, family, and clan. Various data collections are accessible from all levels, including sequence homologs, bibliographies, substrate cleavage sites, and more. Data analysis can reveal peptidase binding site preferences and exclusions, as well as identify instances of cooperative binding between adjacent binding sites.
Article
Chemistry, Applied
Emel Karakilic, Zuhal Alim, Mustafa Emirik, Arif Baran
Summary: Two novel metallophthalocyanines were synthesized and characterized for their solubility and properties, including UV-Vis, FT-IR, and NMR. The compounds exhibited strong inhibitory effects on human erythrocyte carbonic anhydrase isoforms, supported by molecular docking studies. The binding interaction of metallophthalocyanines with enzymes was analyzed in detail.
APPLIED ORGANOMETALLIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
William Karsten, Leonard M. Thomas, Christian Fleming, Priscilla Seabourn, Christina Bruxvoort, Lilian Chooback
Summary: Dihydrodipicolinate synthase (DHDPS) catalyzes the initial step in the biosynthesis of L-lysine, and is a potential drug target due to its absence in mammals. Acetopyruvate is a slow-binding inhibitor of DHDPS that competes with pyruvate to form a covalent enamine complex, confirmed by spectral studies and crystal structure analysis.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Chemistry, Analytical
Wu-Yingzheng Guo, Rong-Rong Li, Yi-Xuan Fu, Shi-Yu Liu, Guo-Zhen Liu, Wen-Chao Yang, Guang-Fu Yang
Summary: PGP-I, identified as a novel inflammatory cytokine, is found to be involved in the development of HCC and could serve as a potential biomarker and therapeutic target for HCC. Bioimaging with a specific biosensor revealed aberrant expression of PGP-I in HCC cells, leading to tumor progression.
ANALYTICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Kyle S. Gregory, Gyles E. Cozier, Sylva L. U. Schwager, Edward D. Sturrock, K. Ravi Acharya
Summary: This study reports the structural basis of domain-specific inhibition of angiotensin-1-converting enzyme (ACE) by lactotripeptides Val-Pro-Pro and Ile-Pro-Pro. The milk-derived lactotripeptides LPP and VPP have shown promising results in reducing hypertension by inhibiting the N- and C-domain of ACE. The resolution of two X-ray crystal structures and kinetic analysis provide important insights into the molecular interactions underlying this inhibition.
Article
Biochemistry & Molecular Biology
Saira Hussain, Ata ur Rehman, David J. Luckett, Syed Muhammad Saqlan Naqvi, Christopher L. Blanchard
Summary: The research focused on purifying protease inhibitors (PIs) from canola meal of genetically diverse Brassica napus genotypes BLN-3347 and Rivette. The purified PIs exhibited diverse functionalities, inhibiting DPP-IV and ACE with differing effectiveness. These PIs have potential applications in human therapy and in breeding for canola disease resistance.
Article
Chemistry, Medicinal
Junius Eugene Thomas, Mi Wang, Wei Jiang, Meilin Wang, Lu Wang, Bo Wen, Duxin Sun, Shaomeng Wang
Summary: The study describes the design, synthesis, and evaluation of potent PROTAC degraders (JET-209) targeting the transcriptional coactivators CBP and p300. JET-209 achieved high degradation potency for CBP and p300 in leukemia cell lines and demonstrated inhibition of tumor growth in xenograft models. JET-209 shows promise as a lead compound for developing CBP/p300 degraders for cancer treatment.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Kamaleddin H. M. E. Tehrani, Nicola Wade, Vida Mashayekhi, Nora C. Bruchle, Willem Jespers, Koen Voskuil, Diego Pesce, Matthijs J. van Haren, Gerard J. P. van Westen, Nathaniel Martin
Summary: The novel cephalosporin prodrugs designed to inhibit metallo-beta-lactamases have shown potential, especially the thiomandelic acid conjugate (8). Conjugate 8 not only effectively inhibits IMP-type MBLs, but also significantly reduces the minimum inhibitory concentration of meropenem against IMP-producing bacteria. These prodrugs act as slowly turned-over substrates to inhibit IMP-type MBLs, with the phenyl and carboxyl moieties of crucial importance for potency.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Yuning Chen, Ya-Nan Zhang, Renhong Yan, Guifeng Wang, Yuanyuan Zhang, Zhe-Rui Zhang, Yaning Li, Jianxia Ou, Wendi Chu, Zhijuan Liang, Yongmei Wang, Yi-Li Chen, Ganjun Chen, Qi Wang, Qiang Zhou, Bo Zhang, Chunhe Wang
Summary: A monoclonal antibody called 3E8 was found to block multiple coronaviruses, including SARS-CoV-2 and its variants, without affecting the physiological activities of ACE2. It also showed effectiveness in blocking SARS-CoV-2 infection and provided a potential broad-spectrum strategy against coronaviruses that use ACE2 as entry receptors.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Article
Peripheral Vascular Disease
Biplab K. Maiti
Summary: The recombinant soluble human angiotensin-converting enzyme 2 (rshACE2) is a promising therapy against SARS-CoV-2 infection, but has drawbacks that reduce its clinical success. Bioengineered ACE2 (Tag-sACE2 and probiotic-ACE2) may be a way to overcome these limitations and address the ongoing pandemic.
JOURNAL OF HUMAN HYPERTENSION
(2022)
Article
Chemistry, Medicinal
Lorenza Fagnani, Lisaurora Nazzicone, Pierangelo Bellio, Nicola Franceschini, Donatella Tondi, Andrea Verri, Sabrina Petricca, Roberto Iorio, Gianfranco Amicosante, Mariagrazia Perilli, Giuseppe Celenza
Summary: This study investigated the inhibitory activity of protocetraric and salazinic acids against SARS-CoV-2 3CL(pro). The results showed that both compounds are slow-binding inactivators of 3CL(pro) with a competitive inhibition mechanism. In cellular experiments, these compounds did not show cytotoxicity. Molecular modeling predicted the binding mechanism of these compounds with 3CL(pro).