Article
Multidisciplinary Sciences
Gonzalo L. Gonzalez-Del Pino, Kunhua Li, Eunyoung Park, Anna M. Schmoker, Byung Hak Ha, Michael J. Eck
Summary: The dysregulation of the RAF/MEK/ERK pathway is associated with many cancers, making the proteins involved, like MEK, a focus of drug discovery efforts. Allosteric MEK inhibitors have complex effects on this pathway and are used in combination with BRAF inhibitors in malignant melanoma. Recent studies suggest that these inhibitors act most potently on BRAF/MEK complexes rather than on free active MEK.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Inorganic & Nuclear
Vishwesh Mishra, Nitish Kumar Sinha, Natesan Thirupathi
Summary: By reacting with Hg(OC(O)CF3)(2), separate reactions of cycloplatinated 2-tolyl- and 2-anisylguanidine complexes yielded a one-dimensional coordination polymer and a discrete tetrametallic complex with different structures and properties. The formation mechanisms and structural characteristics of these products were explained in detail, with important characterization information provided by multinuclear NMR spectroscopy and single-crystal X-ray diffraction studies.
INORGANIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Zilun Hu, Doree Sitkoff, Peter W. Glunz, Yan Zou, Cailan Wang, Jodi K. Muckelbauer, Leonard P. Adam, Ruth R. Wexler, Mimi L. Quan
Summary: Derivatives of lactam, cyclic urea, and carbamate were investigated as replacements for aniline amide in a series of phthalazinone-based ROCK inhibitors. Potent ROCK2 inhibitors, such as compound 22, were identified, demonstrating excellent overall kinase selectivity and good isoform selectivity over ROCK1.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Review
Biochemistry & Molecular Biology
Lianbo Li, Cynthia Meyer, Zhi-Wei Zhou, Ammar Elmezayen, Kenneth Westover
Summary: Allosteric mechanisms are common in nature but rare in human-designed perturbagens. The development of KRAS(G12C) inhibitors suggests that covalent chemistry could expand the use of allosteric inhibitors. This study explores the feasibility of extending this approach to other proteins in the RAS and kinase family, which play important roles in cellular processes, especially in cancer therapy.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anna Barile, Theo Battista, Annarita Fiorillo, Martino Luigi di Salvo, Francesco Malatesta, Angela Tramonti, Andrea Ilari, Roberto Contestabile
Summary: PLP, the active form of vitamin B6, is crucial in metabolism as an enzyme cofactor. In Escherichia coli, PNPO catalyzes PLP formation and is inhibited by the same molecule through allosteric regulation. Crystallographic studies identified the allosteric site of PLP on PNPO, and mutagenesis of the arginine cage can modulate the enzyme's allosteric properties.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Polymer Science
Xiang Shi, Pierre-Antoine Albouy, Pascale Launois
Summary: This study presents a different view that the evolution of X-ray patterns reflects changes in crystalline texture rather than polymorphism. This enables a quantitative description of X-ray fiber patterns but also highlights some fundamental structural issues.
Article
Multidisciplinary Sciences
Dongxue Yang, Eric Gouaux
Summary: This study used cryo-electron microscopy structures to elucidate the structural states of SERT in different conditions, revealing all fundamental steps of the transport cycle. The research identified the substrate-bound allosteric site and provided new structural insights into how SERT controls the binding and unbinding of serotonin.
Article
Biology
Alex Macpherson, Maisem Laabei, Zainab Ahdash, Melissa A. Graewert, James R. Birtley, Monika-Sarah E. D. Schulze, Susan Crennell, Sarah A. Robinson, Ben Holmes, Vladas Oleinikovas, Per H. Nilsson, James Snowden, Victoria Ellis, Tom Eirik Mollnes, Charlotte M. Deane, Dmitri Svergun, Alastair D. G. Lawson, Jean M. H. van den Elsen
Summary: This study investigates the binding of four knob domain peptides with complement C5 and reveals their effects on the target. The research identifies a new allosteric mechanism for inhibiting C5 and expands the therapeutic scope of C5. Additionally, it introduces knob domains as new low molecular weight antibody fragments with therapeutic potential.
Article
Multidisciplinary Sciences
Daisuke Sawada, Yoshiharu Nishiyama, Riddhi Shah, V. Trevor Forsyth, Estelle Mossou, Hugh Michael O'Neill, Masahisa Wada, Paul Langan
Summary: The study reveals that during mercerization of bacterial cellulose, chains fold back on themselves in a zigzag pattern to form crystalline anti-parallel domains. This finding provides important insights into the molecular-level mechanism of this industrial process.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Dominique Laniel, Florian Trybel, Bjoern Winkler, Florian Knoop, Timofey Fedotenko, Saiana Khandarkhaeva, Alena Aslandukova, Thomas Meier, Stella Chariton, Konstantin Glazyrin, Victor Milman, Vitali Prakapenka, Igor A. Abrikosov, Leonid Dubrovinsky, Natalia Dubrovinskaia
Summary: This study presents the chemical and structural diversity of lanthanum hydrides synthesized under high pressure, providing clues for the search of other hydrides and high-temperature superconductors. However, assessing potentially superconducting phases and the nature of electronic transitions remains a challenge.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Marina Abe, Ryo Suzuki, Keiichi Hirano, Haruhiko Koizumi, Kenichi Kojimaa, Masaru Tachibana
Summary: The growth of high-quality protein crystals is essential for protein structure analysis. Twisting is identified as one of the main residual defects in high-quality crystals, determining their perfection. The handedness of twisting may be attributed to the interaction of chiral protein molecules with asymmetric units in crystal forms. This study provides insights into the growth mechanism and control of high-quality crystals.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Medicinal
Jigang Fan, Yaqin Liu, Ren Kong, Duan Ni, Zhengtian Yu, Shaoyong Lu, Jian Zhang
Summary: Allostery is a fundamental mechanism in signal transmission, with allosteric drugs offering unique pharmacological advantages. The experimental approaches for developing allosteric modulators are traditionally serendipitous. The reversed allosteric communication theory provides a feasible tool for unbiased detection of allosteric sites.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Microbiology
Zhiwei Kong, Xin Zhang, Feng Zhou, Liu Tang, Yitong Chen, Saijie Li, Xiaokang Zhang, Letian Kuai, Wenji Su, Weiren Cui, Jiaxi Cai, Yuli Wang, Jun Yang, You-Liang Peng, Dongli Wang, Junfeng Liu
Summary: Rice blast, caused by M. oryzae, is a devastating disease that affects cultivated rice. Chemical control and the discovery of novel fungicide targets are important for managing the disease. Mps1 is a fungal protein that plays a critical role in plant cell wall penetration during infection. A small-molecule inhibitor, A378-0, has been identified to target Mps1 and inhibit the growth of M. oryzae. This discovery suggests that Mps1 and its orthologs can be potential fungicide targets for developing broad-spectrum fungicides.
Article
Chemistry, Inorganic & Nuclear
Ziyan Lv, Rukang Li
Summary: In this study, a tantalum phosphate crystal Na11Ta8P7O43 with a moderate second harmonic response was synthesized using self-fluxes method. The crystal was found to have unique structural features and moderate nonlinear effects. It exhibits phase-matchable second harmonic generation, a shorter cutoff edge than known materials LiTaO3 and KTiOPO4, and high transmittance in the visible to near infrared band, suggesting its potential as a nonlinear optical crystal.
DALTON TRANSACTIONS
(2023)
Article
Chemistry, Inorganic & Nuclear
Ziyan Lv, Rukang Li
Summary: In this study, a tantalum phosphate crystal with a moderate second harmonic response and unique structural features was successfully synthesized. It has the potential to serve as a nonlinear optical crystal.
DALTON TRANSACTIONS
(2023)
Article
Biochemical Research Methods
Constantine Kreatsoulas, Kartik Narayan
ANALYTICAL BIOCHEMISTRY
(2010)
Article
Chemistry, Medicinal
Craig A. Stump, Ian M. Bell, Rodney A. Bednar, John F. Fay, Steven N. Gallicchio, James C. Hershey, Richard Jelley, Constantine Kreatsoulas, Eric L. Moore, Scott D. Mosser, Amy G. Quigley, Shane A. Roller, Christopher A. Salvatore, Steven S. Sharik, Cory R. Theberge, C. Blair Zartman, Stefanie A. Kane, Samuel L. Graham, Harold G. Selnick, Joseph P. Vacca, Theresa M. Williams
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2010)
Article
Chemistry, Medicinal
Vadim Y. Dudkin, Keith Rickert, Constantine Kreatsoulas, Cheng Wang, Kenneth L. Arrington, Mark E. Fraley, George D. Hartman, Yowei Yan, Mari Ikuta, Steven M. Stirdivant, Robert A. Drakas, Eileen S. Walsh, Kelly Hamilton, Carolyn A. Buser, Robert B. Lobell, Laura Sepp-Lorenzino
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2012)
Article
Pharmacology & Pharmacy
Marlene A. Jacobson, Constantine Kreatsoulas, Danette M. Pascarella, Julie A. O'Brien, Cyrille Sur
MOLECULAR PHARMACOLOGY
(2010)
Article
Multidisciplinary Sciences
Lei Ma, Matthew Seager, Marion Wittmann, Marlene Jacobson, Denise Bickel, Maryann Burno, Keith Jones, Valerie Kuzmick Graufelds, Guangping Xu, Michelle Pearson, Alexander McCampbell, Renee Gaspar, Paul Shughrue, Andrew Danziger, Christopher Regan, Rose Flick, Danette Pascarella, Susan Garson, Scott Doran, Constantine Kreatsoulas, Lone Veng, Craig W. Lindsley, William Shipe, Scott Kuduk, Cyrille Sur, Gene Kinney, Guy R. Seabrook, William J. Ray
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2009)
Article
Chemistry, Medicinal
Steven Howard, Nader Amin, Andrew B. Benowitz, Elisabetta Chiarparin, Haifeng Cui, Xiaodong Deng, Tom D. Heightman, David J. Holmes, Anna Hopkins, Jianzhong Huang, Qi Jin, Constantine Kreatsoulas, Agnes C. L. Martin, Frances Massey, Lynn McCloskey, Paul N. Mortenson, Puja Pathuri, Dominic Tisi, Pamela A. Williams
ACS MEDICINAL CHEMISTRY LETTERS
(2013)
Article
Chemistry, Medicinal
Deepak Bandyopadhyay, Constantine Kreatsoulas, Pat G. Brady, Joseph Boyer, Zangdong He, Genaro Scavello, Tyler Peryea, Ajit Jadhav, Dac-Trung Nguyen, Rajarshi Guha
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2019)
Article
Chemistry, Medicinal
Curt D. Haffner, Adam K. Charnley, Christopher J. Aquino, Linda Casillas, Maire A. Convery, Julie A. Cox, Mark A. Elban, Nicole C. Goodwin, Peter J. Gough, Pamela A. Haile, Terry V. Hughes, Beth Knapp-Reed, Constantine Kreatsoulas, Ami S. Lakdawala, Huijie Li, Yiqian Lian, David Lipshutz, John F. Mehlmann, Michael Ouellette, Joseph Romano, Lisa Shewchuk, Arthur Shu, Bartholomew J. Votta, Huiqiang Zhou, John Bertin, Robert W. Marquis
ACS MEDICINAL CHEMISTRY LETTERS
(2019)
Article
Chemistry, Medicinal
Robert M. Garbaccio, Shaei Huang, Edward S. Tasber, Mark E. Fraley, Youwei Yan, Sanjeev Munshi, Mari Ikuta, Lawrence Kuo, Constanine Kreatsoulas, Steve Stirdivant, Bob Drakas, Keith Rickert, Eileen S. Walsh, Kelly A. Hamilton, Carolyn A. Buser, James Hardwick, Xianzhi Mao, Stephen C. Beck, Marc T. Abrams, Weikang Tao, Rob Lobell, Laura Sepp-Lorenzino, George D. Hartman
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2007)
Article
Chemistry, Medicinal
Edward J. Brnardic, Robert M. Garbaccio, Mark E. Fraley, Edward S. Tasber, Justin T. Steen, Kenneth L. Arrington, Vadim Y. Dudkin, George D. Hartman, Steven M. Stirdivant, Bob A. Drakas, Keith Rickert, Eileen S. Walsh, Kelly Hamilton, Carolyn A. Buser, James Hardwick, Weikang Tao, Stephen C. Beek, Xianzhi Mao, Robert B. Lobell, Laura Sepp-Lorenzino, Youwei Yan, Mari Ikuta, Sanjeev K. Munshi, Lawrence C. Kuo, Constantine Kreatsoulas
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2007)
Article
Chemistry, Medicinal
Georgia B. McGaughey, Robert P. Sheridan, Christopher I. Bayly, J. Chris Culberson, Constantine Kreatsoulas, Stacey Lindsley, Vladimir Maiorov, Jean-Francois Truchon, Wendy D. Cornell
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2007)
Article
Chemistry, Medicinal
Mark E. Fraley, Justin T. Steen, Edward J. Brnardic, Kenneth L. Arrington, Keith L. Spencer, Barbara A. Hanney, Yuntae Kim, George D. Hartman, Steven M. Stirdivant, Bob A. Drakas, Keith Rickert, Eileen S. Walsh, Kelly Hamilton, Carolyn A. Buser, James Hardwick, Weikang Tao, Stephen C. Beck, Xianzhi Mao, Robert B. Lobell, Laura Sepp-Lorenzino, Youwei Yan, Mari Ikuta, Sanjeev K. Munshi, Lawrence C. Kuo, Constantine Kreatsoulas
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2006)
Article
Chemistry, Medicinal
Shaei Huang, Robert M. Garbaccio, Mark E. Fraley, Justin Steen, Constantine Kreatsoulas, George Hartman, Steve Stirdivant, Bob Drakas, Keith Rickert, Eileen Walsh, Kelly Hamilton, Carolyn A. Buser, James Hardwick, Xianzhi Mao, Marc Abrams, Steve Beck, Weikang Tao, Rob Lobell, Laura Sepp-Lorenzino, Youwei Yan, Mari Ikuta, Joan Zugay Murphy, Vinod Sardana, Sanjeev Munshi, Lawrence Kuo, Michael Reilly, Elizabeth Mahan
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2006)
Article
Biochemistry & Molecular Biology
Georgia B. McGaughey, J. Chris Culberson, Bradley P. Feuston, Constantine Kreatsoulas, Vladimir Maiorov, Joseph Shpungin
MOLECULAR DIVERSITY
(2006)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
