Results 91 to 100 of about 37,458 (256)

Nucleic Acid Therapeutics for “Undruggable” Cancer Targets: Mechanisms, Challenges, and Prospects

Advanced Science, EarlyView.
Nucleic acid therapeutics bypass the structural limitations of conventional drugs by targeting mRNA rather than proteins. This review examines how antisense oligonucleotides, siRNAs, miRNAs, aptamers, and mRNA vaccines intervene against historically undruggable oncoproteins including Ras, MYC, and p53, highlighting mechanistic advances, delivery ...
Feng Xu, Ke Wang, Kaizhong Lu, Tianlun Hou, Yuan Chen, Xian Wang, Hongchuan Jin   +6 more
wiley   +1 more source

Allosteric Regulation of Photophysics and Binding in Oxazine‐macrocycle Complexes at Single‐molecule Resolution

Angewandte Chemie, EarlyView.
This work explores the interactions between the oxazine dye ATTO655 and two macrocyclic hosts using optical (single‑molecule) spectroscopy. Although ATTO655 forms a classical inclusion complex with cucurbit[8]uril (CB8), its interaction with p‑sulfonatocalix[4]arene (sCX4) leads to the formation of dim exclusion complexes.
Siyu Lu, Thomas‐Otavio Peulen, Hongbin Wu, Florian Lindemann, Despoina Kapiki, Rasmus Linser, Andreas Hennig, Thorben Cordes   +7 more
wiley   +2 more sources

Heat Shock Protein 90: From Molecular Chaperone Function to Therapeutic Targeting in Malignancies

Advanced Science, EarlyView.
In this review, an integrated conceptual framework linking HSP90's molecular chaperone functions to its pathological roles in cancer is proposed. HSP90 serves as a central node that integrates oncogenic signaling, buffers proteotoxic stress, maintains cancer stem cell plasticity, and shapes tumor‐immune interactions, all of which converge to drive ...
Beibei Zhang, Xinxin Zou, Jiansong Zhou, Qinmiao Sun, Dahua Chen   +4 more
wiley   +1 more source

AND‐Logic‐Gated Aptamer Switch for Precise Targeting and Regulation of RNA G‐Quadruplexes

Angewandte Chemie, EarlyView.
An AND‐logic‐gated aptamer switch enables tumor‐selective activation of RNA G‐quadruplex (rG4)‐targeting function. By combining cell‐surface recognition and intracellular redox sensing, the system achieves precise regulation of disease‐relevant RNA structures exclusively in tumor cells, with minimal off‐target effects in normal cells, offering a ...
Dan Wang, Ying Feng, Chun Kit Kwok
wiley   +2 more sources

ProSiteHunter: A Unified Framework for Sequence‐Based Prediction of Protein‐Nucleic Acid and Protein‐Protein Binding Sites

Advanced Science, EarlyView.
This study proposed a unified sequence‐based framework for protein binding site prediction, which adopted a tri‐track semantic multi‐source feature fusion strategy to effectively capture diverse macromolecular interaction sites and further improved the accuracy of antibody‐antigen interaction prediction.
Dongliang Hou, Qihang Zhen, Zexin Lv, Xinyue Cui, Suhui Wang, Minghua Hou, Zhan Zhou, Xiaogen Zhou, Guijun Zhang   +8 more
wiley   +1 more source

DNA‐Induced Entropic Gain Triggers an Allosteric Switch for Biomolecular Condensation of Heat Shock Transcription Factor 1

Angewandte Chemie, EarlyView.
Hsf1 undergoes phase separation around target DNA, activating stress‐responsive transcription. DNA binding tunes conformational dynamics of Hsf1DBD, which propagates through large‐scale domain rearrangements involving DBD–IDR interactions to regulate phase separation. This hierarchical framework illustrates how local structural events at the side chain
Soichiro Kawagoe, Hiroyuki Kumeta, Tomohide Saio   +2 more
wiley   +2 more sources

A Brain‐Penetrant Nanobody Reveals GSK3β‐Driven Proline‐Directed Phosphorylation as a Master Regulator of Ischemic Neurodegeneration

Advanced Science, EarlyView.
A brain‐targeted nanoparticle enables delivery of a therapeutic nanobody (Nb.29E9) that inhibits pathogenic GSK3β signaling. This intervention restores AMPK/mTORC1/TGFβ homeostasis, attenuates neuroinflammation and oxidative stress, and promotes long‐term functional recovery after ischemic stroke.
Lan Li, Muyang Li, Lei Sun, Ying Yang, Yuanshun Wu, Ziyi Yin, Anni Wang, Peiyang Zhou, Shaoxiang Luo, Jian Chen, Jun Qin, Zhibing Ai, Zilong Yuan, Zhiqiang Dong, Min Zhang   +14 more
wiley   +1 more source

Allosteric Inhibition of Polycomb Repressive Complex 2 by an EZH2‐Selective Small Molecule Inhibitor

Advanced Science, EarlyView.
The study characterizes C36, a highly selective EZH2/PRC2 inhibitor that acts via a novel allosteric mechanism. Unlike previous inhibitors, C36 inhibits EZH2/PRC2 by disrupting the allosteric communication between EZH2 and EED in a SAM‐noncompetitive manner.
Ting Cao, Dongdong Liu, Haishan Gao, Chenyang Qin, Wen Zhang, Ziyun Lu, Dongxia Tan, Yuxiu Qu, Yusong Liu, Zhiran Zou, Hongtao Yu, Wei Qi   +11 more
wiley   +1 more source

Free fatty acid receptor 2 allosterism is defined by cellular context

Cell Communication and Signaling
Background Allosteric modulators offer a way to fine-tune GPCR signaling in the presence of endogenous ligands. The short-chain fatty acid receptor FFA2R (GPR43) recognizes propionate and allosteric ligands such as Cmp58 and AZ1729.
Simon Lind, Ayaan Abdi Ali, Sarah Al Hamoud Al Asswad, Volker M. Lauschke, Huamei Forsman, Claes Dahlgren, Linda C. Johansson   +6 more
doaj   +1 more source

A Phase‐Resolved Geometric Deep Learning Framework Maps Structural Determinants of Disease‐Associated Protein Aggregation and Guides Suppressor Design

Advanced Science, EarlyView.
SKALE 2.0 maps disease‐associated protein aggregation as a phase‐resolved structural process, linking mutation‐induced geometric perturbations to nucleation, elongation, and suppressor design. Across neurodegenerative proteins, the framework reveals cryptic aggregation vulnerabilities, separates phase‐concordant and phase‐switching mutations, and ...
Jia Shen Sio, Wei Xuan Wilson Loo, Yan Shan Loo, Wen Xin Tan, Hui Xuan Lim, Huitao Liu, Chen Seng Ng   +6 more
wiley   +1 more source