Article
Chemistry, Medicinal
Shelby R. Kell, Zhen Wang, Haitao Ji
Summary: The study reveals a convergence of binding conformations of alpha-helical hydrophobic hot spots in protein-protein complex structures, regardless of the position along the helix. This observation streamlines the development of pharmacophore models and may be useful for the design of novel alpha-helical hot spot mimetics.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Chenghui Shi, Julia Kaffy, Tap Ha-Duong, Jean-Francois Gallard, Alain Pruvost, Aloise Mabondzo, Lidia Ciccone, Sandrine Ongeri, Nicolo Tonali
Summary: A novel class of peptidomimetic foldamers based on diaza-peptide units is reported, which can undergo helical folding in water and have potential applications in protein-protein interaction and amyloid protein aggregation.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Pancham Lal Gupta, Heather A. Carlson
Summary: In drug design, molecular dynamics calculations of protein-fragment pairs can determine the nearest hot spots, guiding the direction and type of chemical modifications that can improve binding affinity. This method provides a general framework for choosing chemical groups to grow lead molecules and improve drug design.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Chemistry, Medicinal
Zhen Wang, Haitao Ji
Summary: The cooperativity index, Kc, was developed to examine the binding synergy between hot spots of the ligand-protein. The spatial arrangements of hydrophilic alpha-helical hot spots in protein-protein interaction (PPI) complex structures were disclosed and quantified using novel clustering models. The driving force for the convergence of these hot spots was analyzed, allowing the development of pharmacophore models for designing new mimetics.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Green & Sustainable Science & Technology
Meng He, Zhihao Li, Yujie Guo, Maofeng Zhang, Zhengdong Zhu, Xiaoyi Shi, Konghao Han, Youju Huang, Honglin Liu
Summary: Researchers demonstrated a method of shrinking three-dimensional (3D) hot spot droplets on a hydrophobic substrate for the quantitative and multiplex detection of pesticide residues using portable Raman spectrometer. The shrunk droplets, consisting of analyte solution and AgNPs sol, simultaneously increased the density of plasmonic hot spots and immobilized target molecules. The proposed strategy exhibited excellent SERS sensitivity for the analysis of pesticides down to 10(-8) m and achieved quantitative analysis and multi-component detection of pesticide residues on honeysuckle surface.
ADVANCED SUSTAINABLE SYSTEMS
(2023)
Article
Biochemistry & Molecular Biology
Pranesh Padmanabhan, Andrew Kneynsberg, Esteban Cruz, Rumelo Amor, Jean-Baptiste Sibarita, Jurgen Gotz
Summary: We found that Tau exhibits spatial and kinetic heterogeneity near the plasma membrane, forming nanometer-sized hot spots, which are longer-lasting than its interaction with microtubules. These hot spots are different from Tau condensation on microtubules and independent of cholesterol.
Article
Chemistry, Multidisciplinary
Elizaveta P. Kozhina, Sergey A. Bedin, Natalia L. Nechaeva, Sergey N. Podoynitsyn, Vladimir P. Tarakanov, Stepan N. Andreev, Yuriy V. Grigoriev, Andrey V. Naumov
Summary: This paper presents a cost-effective approach for fabricating substrates for surface-enhanced Raman scattering (SERS) with metal nanowires grown in pores of polymer track-etched membranes. The technique allows for synthesis of nanowire arrays with controlled surface density and diameter, with potential applications for effective sensing of extremely low concentration analytes. Experimental results show significant Raman signal enhancement in hot spots between nanowires tips, demonstrating the potential of this SERS technique for sensitive detection.
APPLIED SCIENCES-BASEL
(2021)
Article
Chemistry, Medicinal
Miku Azuma, Manami Inoue, Aya Nishida, Haruka Akahane, Masataka Kitajima, Shunsuke Natani, Ryusei Chimori, Atsushi Yoshimori, Yasunari Mano, Hiromi Uchiro, Sei-ichi Tanuma, Ryoko Takasawa
Summary: In this study, it was found that the carboxy group in TLSC702 was critical for binding with the divalent zinc at the active site of GLO I, while the side chain substituents in the benzene ring had little influence on the inhibition of GLO I. Adding hydrophobic moieties to the phenyl group enhanced the antiproliferative effects of TLSC702 by increasing cell membrane permeability.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Franco Viscarra, Juan Facundo Chrestia, Yaima Sanchez, Edwin G. Perez, Philip C. Biggin, Cecilia Bouzat, Isabel Bermudez, Jhon J. Lopez
Summary: In this study, six new ligands with ether quinuclidines were synthesized and evaluated for their pharmacological activity on α7 nAChR. Ligand 4 activated the receptor, while ligands 5 and 7 had no effect. Ligands 6, 8, and 9 potentiated ACh-induced currents, with ligand 6 being the most potent. Computational studies provided insights into the binding preferences and key interactions of these ligands. Ligand 6 was identified as a novel type I positive allosteric modulator of α7 nAChR.
ACS CHEMICAL NEUROSCIENCE
(2023)
Correction
Plant Sciences
Christopher Hepworth, William H. J. Wood, Tom Z. Emrich-Mills, Matthew S. Proctor, Stuart Casson, Matthew P. Johnson
Summary: The correction to the paper has been published.
Article
Development Studies
Rajat Singh Yadav, Kalluru Siva Reddy
Summary: This paper examines the convergence hypothesis in financial inclusion performance and explores the spatial factors influencing financial inclusion levels in India from 2011 to 2018. The study finds evidence of spatial dependencies in the financial inclusion index across 591 Indian Districts. The convergence results show that low banking services are associated with spatial disparities in distribution of vulnerable populations, and the neighborhood effect exists with the low financially sound population.
JOURNAL OF SOCIAL AND ECONOMIC DEVELOPMENT
(2023)
Article
Chemistry, Organic
Xiaowei Wu, Haitao Ji
JOURNAL OF ORGANIC CHEMISTRY
(2018)
Article
Chemistry, Medicinal
Zhen Wang, Min Zhang, Jin Wang, Haitao Ji
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Multidisciplinary Sciences
Peng Sang, Min Zhang, Yan Shi, Chunpu Li, Sami Abdulkadir, Qi Li, Haitao Ji, Jianfeng Cai
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Biochemistry & Molecular Biology
Qingliang Li, Rezaul M. Karim, Mo Cheng, Mousumi Das, Lihong Chen, Chen Zhang, Harshani R. Lawrence, Gary W. Daughdrill, Ernst Schonbrunn, Haitao Ji, Jiandong Chen
Review
Chemistry, Medicinal
Zhen Wang, Zilu Li, Haitao Ji
Summary: Aberrant activation of the Wnt/beta-catenin signaling pathway is associated with cancer, and direct targeting of beta-catenin is a promising strategy but challenging. Research has identified potential small-molecule binding sites and summarized bioactive small molecules that target beta-catenin directly.
MEDICINAL RESEARCH REVIEWS
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Narges K. Tafreshi, Darpan N. Pandya, Christopher J. Tichacek, Mikalai M. Budzevich, Zhen Wang, Jordan N. Reff, Robert W. Engelman, David C. Boulware, Alberto A. Chiappori, Jonathan R. Strosberg, Haitao Ji, Thaddeus J. Wadas, Ghassan El-Haddad, David L. Morse
Summary: The study demonstrates significant potential for the clinical translation of [Ac-225]Ac-DOTA-TATE for lung NENs, showing notable tumor growth delay and prolonged time to experimental endpoint.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2021)
Article
Chemistry, Medicinal
Zhen Wang, Min Zhang, Wen Luo, Yongqiang Zhang, Haitao Ji
Summary: The study presents a new small-molecule inhibitor that selectively disrupts the beta-catenin/BCL9 interaction, inhibits the role of the Wnt signaling pathway in cancer, and can serve as a lead compound for further optimization.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Zhen Wang, Min Zhang, Victor Quereda, Sylvia M. Frydman, Qianqian Ming, Vincent C. Luca, Derek R. Duckett, Haitao Ji
Summary: This study introduces a drug-like small molecule, ZW4864, which selectively disrupts the protein-protein interaction between BCL9 and beta-catenin, effectively suppressing beta-catenin signaling activation and target gene expression in a mouse model. This provides a potential therapeutic target for developing drugs targeting aberrant Wnt/beta-catenin signaling in diseases such as cancer.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Zilu Li, Min Zhang, Kevin B. Teuscher, Haitao Ji
Summary: Structure-based design and optimization led to the discovery of a small-molecule beta-catenin/BCL9 inhibitor ZL3138, which disrupts the protein-protein interaction effectively and selectively in living cells, showing potential anti-tumor activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Tao Xiao, Luxin Sun, Min Zhang, Zilu Li, Eric B. Haura, Ernst Schonbrunn, Haitao Ji
Summary: A monocarboxylic inhibitor was designed and synthesized to disrupt the protein-protein interaction between GRB2 and phosphotyrosine-containing proteins. Biochemical studies showed compound 7 binds with the SH2 domain of GRB2 with higher potency, while X-ray crystallographic studies revealed key structural features for GRB2-inhibitor binding. This compound with a -1 formal charge offers a new direction for generating cell-permeable inhibitors for the aberrant Ras-MAPK signaling cascade.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Medicinal
Zhen Wang, Haitao Ji
Summary: The cooperativity index, Kc, was developed to examine the binding synergy between hot spots of the ligand-protein. The spatial arrangements of hydrophilic alpha-helical hot spots in protein-protein interaction (PPI) complex structures were disclosed and quantified using novel clustering models. The driving force for the convergence of these hot spots was analyzed, allowing the development of pharmacophore models for designing new mimetics.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
Zhen Wang, Min Zhang, Harriet M. Thompson, Haitao Ji
Summary: A series of new small-molecule beta-catenin/B-cell lymphoma 9 (BCL9) protein-protein interaction inhibitors were reported. Among them, compound 21 showed potent inhibition in cellular context and demonstrated higher potential in regulating transcription and expression of beta-catenin target genes and suppressing survival of beta-catenin-dependent cancer cells.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Shelby R. Kell, Zhen Wang, Haitao Ji
Summary: Fragment-based ligand discovery (FBLD) is a successful approach for designing small-molecule protein-protein interaction (PPI) inhibitors. This article describes a computational protocol using fragment hopping for developing small-molecule PPI inhibitors and includes a case study to illustrate its efficiency. Fragment hopping enables the design of PPI inhibitors based solely on key binding features in the PPI complex structure. This approach is an open system that can incorporate different programs and software to improve its performance.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)