Review
Chemistry, Multidisciplinary
J. Miguel Mata, Edith van der Nol, Sebastian J. J. Pomplun
Summary: Discovering new bioactive molecules is crucial for drug development, and affinity selection based technologies have revolutionized the hit discovery process. Recent breakthroughs in screening ultralarge synthetic peptidomimetic libraries using barcode-free tandem mass spectrometry decoding have enabled hit discovery from libraries with over 100 million members. This technology combines combinatorial synthesis, affinity selection, automated de novo peptide sequencing algorithms, and advances in mass spectrometry instrumentation. Success stories include the discovery of high affinity binders for various drug targets and specific functions and reactivity of synthetic peptidomimetics. This technology is predicted to rapidly evolve and become a broadly used drug discovery technology.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Physical
Ye Sheng, Tingting Deng, Pengfei Qiu, Xun Shi, Jinyang Xi, Yuexing Han, Jiong Yang
Summary: This study presents an example of using high-throughput methods to search for novel Cu-Sn-S ternary thermoelectric materials, involving synthesis, characterization, and analysis. Different strategies were proposed to classify different areas in the images and two interesting thermoelectric phases, Cu7Sn3S10 and Cu1.6S, were identified with potential for high thermoelectric efficiency.
CHEMISTRY OF MATERIALS
(2021)
Article
Chemistry, Medicinal
Xinting Li, Timothy W. Craven, Paul M. Levine
Summary: Cyclic peptides, with their diverse architectures, show potential in intervening and regulating challenging targets. Various screening technologies can be used to generate cyclic peptide libraries for drug research in modern medicine.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Carlo Baggio, Anna Kulinich, Cassandra N. Dennys, Rochelle Rodrigo, Kathrin Meyer, Iryna Ethell, Maurizio Pellecchia
Summary: The study utilized an innovative NMR-guided screening and ligand design approach to derive low-molecular-weight ligands capable of mimicking interactions elicited by ephrin ligands. These agents demonstrated nanomolar affinity, activated receptors in cellular assays with motor neurons, and provided significant motor neuron protection from ALS patient-derived astrocytes. Structural studies on the complex between the ligand-binding domain and the most active agent offered insights into the agents' mechanism at a molecular level, forming a strong foundation for potential treatment of ALS and other human diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Organic
Grzegorz Wolczanski, Wojciech Gil, Jakub Cichos, Marek Lisowski, Piotr Stefanowicz
Summary: Alkyl thiocyanurates, formed by the SN reaction between thiocyanuric acid and alkyl halides, can undergo transthioesterification and ligation with cysteamine-containing molecules, similar to the native chemical ligation of thioesters with peptides containing an N-terminal cysteine moiety. The ligation is irreversible, leading to predominantly mono- and disubstituted products. In contrast, transthioesterification is fully reversible and can be used in constructing dynamic systems. The reactivity of thiocyanurates towards cysteamines and thiols has been explained using conceptual DFT.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Zhihong Liu, Dane Huang, Shuangjia Zheng, Ying Song, Bingdong Liu, Jingyuan Sun, Zhangming Niu, Qiong Gu, Jun Xu, Liwei Xie
Summary: The pre-trained self-attentive message passing neural network (P-SAMPNN) model was developed based on anti-osteoclastogenesis dataset for virtual screening. The model outperformed other baseline models and resulted in the identification of two nanomolar-level inhibitors against osteoclastogenesis with a new scaffold. Subsequent studies showed that these compounds significantly suppressed the expression of specific genes.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Lanlan Jing, Wenxiu Wei, Bairu Meng, Fabien Chantegreil, Florian Nachon, Ana Martinez, Gaochan Wu, Huajun Zhao, Yuning Song, Dongwei Kang, Xavier Brazzolotto, Peng Zhan, Xinyong Liu
Summary: Compounds 39 and 43, derived from tacrine derivatives, are highly selective and potent inhibitors of BuChE, showing improved inhibitory activity and selectivity compared to the lead compound A3Q12. They are also able to inhibit A beta 1-42 peptide self-induced aggregation and have potential as drug candidates for Alzheimer's disease.
BIOORGANIC CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Chen Wang, Michael P. O'Hagan, Ehud Neumann, Rachel Nechushtai, Itamar Willner
Summary: This study introduces nucleic acid-based constitutional dynamic networks (CDNs) that enable control of various catalytic processes, but achieving intercommunication between different CDNs to mimic complex cell biology networks is challenging.
NATURE COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Mahmoud Kandeel, Mizuki Yamamoto, Byoung Kwon Park, Abdulla Al-Taher, Aya Watanabe, Jin Gohda, Yasushi Kawaguchi, Kentaro Oh-hashi, Hyung-Joo Kwon, Jun-ichiro Inoue
Summary: A highly potent set of peptides was designed to prevent MERS-CoV fusion through competition with HR2 at its HR1 binding site. These peptides demonstrated strong inhibition of MERS-CoV cell-cell fusion and plaque formation, with no cytotoxic effects at high concentrations, suggesting their potential as promising antiviral agents.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Analytical
Clara Davoine, Alissia Pardo, Lionel Pochet, Marianne Fillet
Summary: Affinity capillary electrophoresis is an effective method for detecting binders, determining dissociation constants, and characterizing fragment binding sites. This method can provide valuable information to medicinal chemistry projects.
ANALYTICAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Kaijian Bi, Junfei Cheng, Shipeng He, Yuxin Fang, Min Huang, Chunquan Sheng, Guoqiang Dong
Summary: This study designed and synthesized a series of new von Hippel-Lindau (VHL)-recruiting NAMPT-targeting PROTACs using the proteolysis-targeting chimera (PROTAC) technology. A highly potent NAMPT degrader (B3) was successfully identified, which showed excellent degradation activity and antiproliferative potency against A2780 cells. This study provides a highly effective VHL-recruiting NAMPT degrader for the treatment of ovarian cancer.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Vijil Chenthamarakshan, Samuel C. Hoffman, C. David Owen, Petra Lukacik, Claire Strain-Damerell, Daren Fearon, Tika R. Malla, Anthony Tumber, Christopher J. Schofield, Helen M. E. Duyvesteyn, Wanwisa Dejnirattisai, Loic Carrique, Thomas S. Walter, Gavin R. Screaton, Tetiana Matviiuk, Aleksandra Mojsilovic, Jason Crain, Martin A. Walsh, David I. Stuart, Payel Das
Summary: We validate the broad utility of a deep generative framework trained on protein sequences, small molecules, and their interactions to discover inhibitors for emerging drug-target proteins. By using protein sequence-conditioned sampling, we successfully designed small-molecule inhibitors for two dissimilar targets without knowing their structures or active molecules. In vitro experiments showed micromolar-level inhibition for two out of four synthesized candidates for each target. The most potent inhibitor also exhibited activity against several variants in live virus neutralization assays, demonstrating the effectiveness and efficiency of the generative foundation model in accelerated inhibitor discovery without target structure or binder information.
Article
Chemistry, Medicinal
Xiaoyuan Li, Yuexiang Li, Shiyong Fan, Ruiyuan Cao, Xiaojia Li, Xiaomeng He, Wei Li, Longfa Xu, Tong Cheng, Honglin Li, Wu Zhong
Summary: A series of novel quinoline analogues targeting VP1 were identified as potent anti-EV-D68 agents through virtual screening and rational design. Compound 19 exhibited strong antiviral activity against various EV-D68 strains and inhibited viral replication. Mechanistic studies indicated that these anti-EV-D68 agents mainly work by interacting with VP1.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Daniel L. Priebbenow, Mitch Mathiew, Da-Hua Shi, Jitendra R. Harjani, Julia G. Beveridge, Marina Chavchich, Michael D. Edstein, Sandra Duffy, Vicky M. Avery, Robert T. Jacobs, Stephen Brand, David M. Shackleford, Wen Wang, Longjin Zhong, Given Lee, Erin Tay, Helena Barker, Elly Crighton, Karen L. White, Susan A. Charman, Amanda De Paoli, Darren J. Creek, Jonathan B. Baell
Summary: A series of novel 3,3'-disubstituted-5,5'-bi(1,2,4-triazine) compounds with potent in vitro activity against Plasmodium falciparum parasites were recently discovered. The new structure-activity relationship investigation led to the identification of second-generation highly potent antimalarial bis-triazines, with improved in vitro metabolic stability and a fast-killing profile. This new class of orally available antimalarial compounds is of considerable interest.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Mladen Koravovic, Anand Mayasundari, Gordana Tasic, Fatemeh Keramatnia, Timothy R. Stachowski, Huarui Cui, Sergio C. Chai, Barbara Jonchere, Lei Yang, Yong Li, Xiang Fu, Ryan Hiltenbrand, Leena Paul, Vibhor Mishra, Jeffery M. Klco, Martine F. Roussel, William CK. Pomerantz, Marcus Fischer, Zoran Rankovic, Vladimir Savic
Summary: An X-ray structure of a CLICK chemistry-based BET PROTAC bound to BRD2(BD2) inspired the synthesis of JQ1 derived heterocyclic amides. These compounds displayed improved profiles compared to JQ1 and birabresib as potent BET inhibitors. A specific compound 1q (SJ1461) showed excellent affinity to both BRD4 and BRD2 and high potency in acute leukaemia and medulloblastoma cell lines. The co-crystal structure of 1q with BRD4-BD1 revealed polar interactions, explaining the observed affinity improvements. Furthermore, pharmacokinetic studies suggested that the heterocyclic amide moiety improved drug-like features. Our study led to the discovery of the potent and orally bioavailable BET inhibitor 1q (SJ1461) as a promising candidate for further development.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Alexander M. Prophet, Kritanjan Polley, Gary J. Van Berkel, David T. Limmer, Kevin R. Wilson
Summary: The oxidation kinetics of iodide by ozone at the air-water interface is studied in single microdroplets. Molecular simulations and kinetic modeling are used to understand the underlying multiphase mechanism.
Article
Chemistry, Multidisciplinary
Rong Zhang, Jiajing Lan, Fei Wang, Shumei Chen, Jian Zhang
Summary: By utilizing 1,1'-ferrocene dicarboxylic acid as a chelating and surface protection ligand, we have synthesized multi-nuclear indium oxide clusters with varying nuclear sizes, including heptanuclear and thirteen-nuclear clusters. These clusters possess labile coordination sites, allowing for structural modification and self-assembly, resulting in the formation of various cluster structures.
Article
Chemistry, Multidisciplinary
Hui Wang, Hui Liu, Mingsen Wang, Jiaheng Hou, Yongjun Li, Yuancheng Wang, Yingjie Zhao
Summary: Two supramolecular complexes were prepared using CBs and M1, and their single-crystal structures were analyzed by SCXRD. The unexpected 1:2 self-assembly structure between M1 and CB[8] was discovered for the first time. These complexes exhibit unique photophysical properties and provide valuable information about the structure and photophysical properties of supramolecular complexes.
Article
Chemistry, Multidisciplinary
Chang-Hee Lee, Sookil Park, Sanggil Kim, Ji Young Hyun, Hyun Soo Lee, Injae Shin
Summary: The epidermal growth factor receptor (EGFR) is a cell-surface glycoprotein involved in cell proliferation and tumor development. This study used a fluorescently labeled EGFR to investigate its time-dependent endocytosis in live cells and found that appended glycans affect EGFR internalization. Additionally, the study detected sialic acid residues attached to EGFR on the live cell surface using FRET-based imaging. This research provides valuable insights into the cellular functions of EGFR.
Article
Chemistry, Multidisciplinary
Subhankar Sahu, Lokesh Kumar, Sumita Das, Dipti Gupta, Ruchi Anand
Summary: This study proposes a strategy that combines organic electronics with biosensor scaffolds to create a compact device for monitoring environmental aromatic pollution. By coupling biosensing protein MopR with an organic electrochemical transistor (OECT), a sensor module capable of efficient detection of phenol was designed. Exclusive phenol detection with minimal loss of sensitivity could be achieved in complex pollutant mixtures and real environmental samples.
Review
Chemistry, Multidisciplinary
Changseok Lee, Hyung-Joon Kang, Sungwoo Hong
Summary: The formation of C-N bonds through hydroamination reactions catalyzed by nickel hydrides has been a topic of recent interest. This approach offers a way to efficiently transform a variety of alkene and alkyne substrates into compounds enriched with C-N bonds. The review provides a concise overview of the underlying reaction mechanisms and aims to stimulate further progress in NiH-catalytic techniques and catalyst design.
Article
Chemistry, Multidisciplinary
Yueci Wu, Lu-Lu Sun, Hai-Hao Han, Xiao-Peng He, Weiguo Cao, Tony D. James
Summary: Drug-induced liver injury (DILI) is a common cause of acute liver failure in the USA and Europe, but most cases can be recovered or prevented by discontinuing the offending drug. Recent research has found that peroxynitrite (ONOO-) can be used as a potential indicator for early diagnosis of DILI, and there is an urgent need to establish a method to detect and track peroxynitrite in DILI cases. In this study, a FRET-based nano fluorescent probe CD-N-I was developed, which showed high selectivity and sensitivity in detecting peroxynitrite. The probe successfully detected exogenous peroxynitrite in live cells and endogenous peroxynitrite in APAP-induced liver injury of HepG2 cells.
Article
Chemistry, Multidisciplinary
Dmitry L. Lipilin, Mikhail O. Zubkov, Mikhail D. Kosobokov, Alexander D. Dilman
Summary: This article describes a direct photocatalytic method for the thiolation of unprotected acids, which was previously challenging. By using a thionocarbonate reagent with an N-O bond, the efficient conversion of carboxylic acids to thiols is achieved.
Article
Chemistry, Multidisciplinary
Jason Malenfant, Lucille Kuster, Yohann Gagne, Kouassi Signo, Maxime Denis, Sylvain Canesi, Mathieu Frenette
Summary: Raman microscopy can reveal compound-specific vibrational fingerprints without sample preparation. The combination of efficient theoretical calculations and a user-friendly software can accurately predict peak positions and provide match scores to assist with structure determination.
Article
Chemistry, Multidisciplinary
Jayoh A. Hernandez, Paul S. Micus, Sean Alec Lois Sunga, Luca Mazzei, Stefano Ciurli, Gabriele Meloni
Summary: Essential trace metals play crucial roles in the survival and virulence of bacterial pathogens. Helicobacter pylori requires nickel for colonization and persistence in the stomach, and NixA is an essential nickel transporter in this process. This study characterizes the selectivity and electrogenic nature of NixA-mediated nickel transport.
Article
Chemistry, Multidisciplinary
Tarali Devi, Kuheli Dutta, Jennifer Deutscher, Stefan Mebs, Uwe Kuhlmann, Michael Haumann, Beatrice Cula, Holger Dau, Peter Hildebrandt, Kallol Ray
Summary: This study emphasizes the importance of subtle electronic changes and secondary interactions in the stability of biologically relevant metal-dioxygen intermediates. It also shows that the role of the chloride ligand in stabilizing the Fe-III-(OOBu)-Bu-t moiety can extend to other anions, including the thiolate ligand.
Article
Chemistry, Multidisciplinary
Jacqueline R. Santhouse, Jeremy M. G. Leung, Lillian T. Chong, W. Seth Horne
Summary: By studying the folding kinetics and mechanism of the BdpA sequence, researchers found that altering the backbone connectivity can affect protein folding. This suggests that protein mimetic chains have a significant degree of plasticity in transitioning between unfolded and folded states.
Article
Chemistry, Multidisciplinary
Divanshu Gupta, Ralf Einholz, Holger F. Bettinger
Summary: This study presents the first direct spectroscopic evidence of a cyclic seven-membered iminoborane. Compared to linear amino-iminoboranes, this cyclic iminoborane exhibits weakened bond strength and lower Lewis acidity value. The study suggests that the reduced ring strain of cyclic iminoborane prevents nitrogen fixation but allows facile (2 + 2) cycloaddition reaction with C2H4.
Article
Chemistry, Multidisciplinary
Renny Mathew, Aniruddha Mazumder, Praveen Kumar, Julie Matula, Sharmarke Mohamed, Petr Brazda, Mahesh Hariharan, Brijith Thomas
Summary: This study reveals the packing arrangement of partially disordered nitro-perylenediimide (NO2-PDI) using a synergistic approach that combines 3D ED, ssNMR, and DFT techniques. By overcoming these challenges, this methodology opens up new avenues for material characterization, driving exciting advancements in the field.